Fertility and Sterility

The use of arrays in preimplantation genetic diagnosis and screening

Joyce C. Harper, Gary Harton — 2010-06-24

Background: In preimplantation genetic diagnosis (PGD), polymerase chain reaction has been used to detect monogenic disorders, and in PGD/preimplantation genetic screening (PGS), fluorescence in situ hybridization (FISH) has been used to analyze chromosomes. Ten randomized controlled trials (RCTs) using FISH-based PGS on cleavage-stage embryos and one on blastocyst-stage embryos have shown that PGS does not increase delivery rates. Is the failure of PGS due to a fundamental flaw in the idea, or are the techniques that are being used unable to overcome their own, inherent flaws? Array-based technology allows for analysis of all of the chromosomes. Two types of arrays are being developed for use in PGD; array comparative genomic hybridization (aCGH) and single nucleotide polymorphism–based (SNP) arrays. Each array can determine the number of chromosomes, however, SNP-based arrays can also be used to haplotype the sample.Objective(s): To describe aCGH and SNP array technology and make suggestions for the future use of arrays in PGD and PGS.Conclusion(s): If array-based testing is going to prove useful, three steps need to be taken: [1] Validation of the array platform on appropriate cell and tissue samples to allow for reliable testing, even at the single-cell level; [2] deciding which embryo stage is the best for biopsy: polar body, cleavage, or blastocyst stage; [3] performing RCTs to show improvement in delivery rates. If RCTs are able to show that array-based testing at the optimal stage for embryo biopsy increases delivery rates, this will be a major step forward for assisted reproductive technology patients around the world.

2009 H1N1 influenza prevention and treatment: counseling infertility patients

Connie E. Alford, Grace L. Chen, Alicia Y. Armstrong — 2010-06-24

It is known that pregnant women are at high risk for complications from the 2009 H1N1 influenza virus. Reproductive endocrinologists often have the opportunity to evaluate patients before conception and are able to counsel them before they become part of this high-risk obstetrics group. The 2009 H1N1 vaccine data and the current recommendations by the Centers for Disease Control and Prevention, American College of Obstetrics and Gynecology, and American Society of Reproductive Medicine are discussed. There is universal agreement in recommending vaccination for all pregnant women and all women attempting conception. Patients should be counseled regarding the vaccine and consider delaying conception until the immunization has been received.

Storage of cryopreserved reproductive tissues: evidence that cross-contamination of infectious agents is a negligible risk

2009-05-29

A misconception in the field of reproductive medicine is that there is a significant risk of cross-contamination during gamete or embryo cryostorage. This article is a review of the available literature on animal models and human IVF and it suggests otherwise. There is a negligible risk of cross-contamination in IVF working conditions.

Analysis of pain and satisfaction with office-based hysteroscopic sterilization

Mark Levie, Gil Weiss, Bente Kaiser, Jennifer Daif, Scott G. Chudnoff — 2009-08-14

Objective: To assess pain and patient satisfaction with office-based hysteroscopic sterilization.Design: This prospective, observational study was designed to assess patient pain perception and satisfaction with office-based hysteroscopic sterilization using the Essure device (Conceptus, Mountain View, CA).Setting: Faculty practice office at an inner-city urban medical center.Patient(s): Women seeking hysteroscopic sterilization.Intervention(s): Office hysteroscopic sterilization under local anesthesia.Main Outcome Measure(s): Pain assessed at the time of the procedure by a 0–10 visual scale and satisfaction by a 1–5 scale.Result(s): From June 2003 to June 2006, 209 patients were recruited. The mean scores for average procedural pain, most procedural pain, and average menstrual pain were 2.6 ± 2.1, 3.3 ± 2.5, and 3.6 ± 2.6, respectively. Standardized pain scores revealed that 149 subjects (70%) experienced average pain that was less than or equal to the pain experienced with their menses. Mean satisfaction rating for the procedure was 4.7 ± 0.71.Conclusion(s): Office-based hysteroscopic sterilization performed with local anesthesia alone is well tolerated, and patients are satisfied with this method for permanent sterilization.

Suppression of ovarian function by a combined oral contraceptive containing 0.02 mg ethinyl estradiol and 2 mg chlormadinone acetate given in a 24/4-day intake regimen over three cycles

Jürgen Spona, Natascha Binder, Kornelia Höschen, Wilfried Feichtinger — 2009-08-25

Objective: To describe the suppression of ovarian function with 0.02 mg ethinyl E2–2 mg chlormadinone acetate administered in a 24/4-day intake regimen in healthy women.Design: Open, uncontrolled, multiple dosing, phase II trial.Setting: Single clinic.Patient(s): Forty women treated.Intervention(s): Treatment for up to three cycles with 0.02 mg ethinyl E2–2 mg chlormadinone acetate given in a 24/4-day regimen.Main Outcome Measure(s): Assessments of ovarian function classified by the Hoogland and Skouby score, thickness of endometrium, cervical reaction, and sex hormone levels, as well as overall tolerability.Result(s): No ovulation was observed in the per protocol set (N = 36), and one in the full analysis set (N = 38) after vomiting and diarrhea. Absence of ovarian activity, residual ovarian activity, and formation of a luteinized unruptured follicle were observed in 75.0%, 15.9%, and 1.1% of medication cycles, respectively. Endometrial thickness was suppressed to 4 to 5 mm compared with 10 to 12 mm without medication. Cervical reaction was negative. Hormone levels were lower with medication than without, and the medication was well tolerated. Treatment-related adverse events were typical of those associated with hormonal contraceptive use.Conclusion(s): Follicular development, cervical reaction, and endometrial thickness were suppressed profoundly after 0.02 mg ethinyl E2–2 mg chlormadinone acetate administration in a 24/4-day regimen, resulting in inhibition of ovulation and unfavorable conditions for fertilization, implantation, and thus pregnancy.

Reproducibility of the interpretation of pelvic x-ray 3 months after hysteroscopic sterilization with Essure

Sebastiaan Veersema, Ben W.J. Mol, Hans A.M. Brölmann — 2009-06-22

Objective: To estimate the diagnostic accuracy and the interobserver reproducibility of pelvic x-rays in the diagnosis of successful bilateral sterilization with Essure after a 3-month follow-up period.Design: Interobserver study.Setting: Outpatient department of obstetrics and gynecology in a Dutch teaching hospital.Patient(s): Patients with successful bilateral Essure placement.Intervention(s): Hysteroscopic sterilization with Essure and pelvic x-ray and hysterosalpingography after a 3-month follow-up period.Main Outcome Measure(s): Six observers evaluations of 47 pelvic x-rays from 47 patients 3 months after a technical successful bilateral placement of microinserts to estimate the reliability of the sterilization. Diagnostic accuracy of pelvic x-ray per observer in detecting incorrectly positioned microinserts was expressed in terms of sensitivity and specificity, with hysterosalpingography as the reference strategy. Reproducibility of the interpretation of the pelvic x-ray was expressed as κ-values.Result(s): The sensitivity and specificity for x-rays read by gynecologists was 0.67 (95% confidence interval [CI], 0.29–0.96) and 0.79 (95% CI, 0.58–1.00) and for radiologists 1.0 and 0.5 (95% CI, 0.36–0.64). The interobserver agreement in reliability of pelvic x-ray of hysteroscopic sterilization assessment with Essure ranged from slight (κ-value = 0.09) for gynecologists to moderate (κ-value = 0.52) for radiologists.Conclusion(s): Test characteristics of pelvic x-ray as the imaging technique to assess the position of the Essure microinserts and tubal patency were poor, as was the reproducibility, particularly if gynecologists performed the evaluation. We do not recommend the use of pelvic x-ray for the assessment of the positioning of microinserts after hysteroscopic sterilization.

Conception probabilities at different days of menstrual cycle in Chinese women

2009-07-06

Objective: To investigate the conception probability among Chinese women.Design: Prospective observational study.Setting: Clinics in hospitals and family planning institutes in 10 provinces and cities.Patient(s): A total of 851 healthy married women aged 18–35 years with normal menstrual cycles who wish to have babies and with no contraception.Intervention(s): Urinary LH was measured around days of expected ovulation for 7 days. The Barrett and Marshall model was used for calculation of conception probabilities on each cycle day from day −5 to day +1 in women with multiple episodes of intercourse.Main Outcome Measure(s): Pregnancies in 1, 3, and ≥6 months.Result(s): A total of 851 women with 2,055 cycles were analyzed. In 489 cycles there was only one episode of intercourse. A total of 601 pregnancies occurred. The conception probabilities from days in relation to ovulation −5 to +1 for a single episode of intercourse were 0.216, 0.102, 0.236, 0.233, 0.388, 0.293, and 0.386, respectively, and for multiple episodes they were 0.254, 0.271, 0.293, 0.365, 0.315, and 0.284, respectively, with the peak value at day −1. Recalculation of the efficacy of emergency contraception with low-dose mifepristone with the present conception probabilities showed higher efficacy.Conclusion(s): Conception probabilities among Chinese women are different from those in the literature. Further comparative studies are needed to confirm an ethnic difference.

The molecular signature of endometriosis-associated endometrioid ovarian cancer differs significantly from endometriosis-independent endometrioid ovarian cancer

2009-07-30

Objective: To determine whether endometriosis-associated endometrioid cancer (EAOC) is a specific entity compared with endometrioid cancer not associated with endometriosis (OC).Design: Case-control study.Setting: University hospital research laboratory.Patient(s): Seven patients with endometriosis-associated ovarian cancer EAOC and five patients each with OC, ovarian endometriosis, and benign ovaries.Intervention(s): Ovarian tissue samples were collected from surgical procedures.Main Outcome Measure(s): We hybridized cRNA samples to the Affymetrix HG-U133A microarray chip. Representative genes were validated by real time polymerase chain reaction.Result(s): We identified two main groups of genes: The first group contained the genes SICA2, CCL14, and TDGF1. These genes were equally regulated in endometriosis and EAOC but not in OC and benign ovaries. The second group contained the genes StAR, SPINT1, Keratin 8, FoxM1B, FOLR1, CRABP1, and Claudin 7. They were equally regulated in EAOC and OC but not in ovarian endometriosis and benign ovaries.Conclusion(s): That the first group is composed of the cytokines SICA2 and CCL14 and the growth factor TDGF1 indicates that the regulation of the autoimmune system and of inflammatory cytokines may be very important in the etiology of endometriosis and EAOC. That the second group is composed of genes that play a central role in cell-cell interaction, differentiation, and cell proliferation indicates that they may be important in the development of ovarian cancer in women with endometriosis.

Laparoscopic conservative surgery for stage IV symptomatic endometriosis: short-term surgical complications

2009-12-07

Objective: To study severe endometriosis as a cause of pelvic pain, which represents one of the most challenging disorders in gynecology.Design: Retrospective study.Setting: Teaching hospital.Patient(s): A total of 1,363 women with severe endometriosis (revised American Society for Reproductive Medicine [rASRM] stage IV).Interventions: A detailed survey of all patients with severe endometriosis (rASRM stage IV) who underwent laparoscopy at our center between January 2004 and December 2007 was carried out.Main Outcome Measure(s): Clinical and surgical data were retrieved and assessed according to the extent of surgery performed. Intraoperative, ultra-short, and short-term clinical complications were assessed.Results: A total of 1,201 women underwent laparoscopic radical surgery with excision of all visible endometriotic lesions, with a significant improvement of symptoms at 1-month follow-up evaluation. The overall intraoperative complication rate was 2.0%. The morbidity was significantly increased when bowel surgery was performed, with a risk of intraoperative complications that was threefold higher. Of the patients who had bowel surgery, 18 (4.1%) required reintervention within the first week after surgery.Conclusion(s): We report on the safety and efficacy of laparoscopic eradication of all visible implants in cases of rASRM stage IV endometriosis when surgery is performed in a referral center.

Understanding adenomyosis: a case control study

F. Andrei Taran, Amy L. Weaver, Charles C. Coddington, Elizabeth A. Stewart — 2009-07-30

Objective: To elucidate the clinical profile of adenomyosis by comparison with uterine leiomyomas.Design: Retrospective case-control study.Setting: Academic medical center.Patient(s): The study comprised 76 women undergoing hysterectomy with adenomyosis and 152 women with uterine leiomyomas but no adenomyosis.Intervention(s): Retrospective medical record review of hospital and ambulatory records.Main Outcome Measure(s): Comparison of women undergoing hysterectomy with a sole pathologic finding of adenomyosis and women with leiomyomas alone.Result(s): Adenomyosis was independently associated with younger age (41.1 years vs. 44.3 years), history of depression (57.1% vs. 24.7%), dysmenorrhea (65.7% vs. 42.3%), and pelvic pain (52.9% vs. 21.1%) in a multivariable unconditional logistic regression analysis compared with women with leiomyomas, where women from both groups had gynecologic symptoms. Furthermore, in a second multivariate model where all subjects had uteri weighing >150 g, women with adenomyosis were more likely to have a history of depression (52.6% vs. 22.2%) and endometriosis (26.3% vs. 2.8%) compared with women with leiomyomas.Conclusion(s): Women undergoing hysterectomy with a histologic diagnosis of adenomyosis have a distinct symptomatology and medical history compared with women with leiomyomas. Better understanding of this disease is required to improve diagnosis and management.

Immunohistochemical detection of aquaporin expression in eutopic and ectopic endometria from women with endometriomas

2009-11-19

Objective: To investigate the expression of aquaporin (AQP) in eutopic and ectopic endometrial tissues from women with endometriomas.Design: Controlled laboratory research.Setting: Hospital-based unit for gynecology and obstetrics and research laboratories.Patient(s): Premenopausal women undergoing laparoscopy for endometriomas.Intervention(s): Endometrial biopsy samples obtained from 70 women with endometriomas.Main Outcome Measure(s): Semiquantitative analysis by immunohistochemistry.Result(s): Aquaporins 2, 5, and 8 were mainly located in luminal and glandular epithelia. The frequency of positive immunostaining for aquaporins 2, 5, and 8 decreased in ectopic compared with eutopic endometria. Aquaporins 2, 5, and 8 were found at a low frequency in the endometria in early proliferative phases but at a higher frequency in late proliferative and secretory phases. There were no significant differences in the menstrual cycle of the proliferative phase and secretory phase in the two groups.Conclusion(s): Aquaporins 2, 5, and 8 were expressed with greater frequency in eutopic endometrial cells than inectopic endometrial cells, suggesting that eutopic endometrial cells have stronger migration activity than ectopic endometrial cells in women with endometriosis.

A novel mutation of HOXA13 in a family with hand-foot-genital syndrome and the role of polyalanine expansions in the spectrum of Müllerian fusion anomalies

Elisa M. Jorgensen, Jane I. Ruman, Leo Doherty, Hugh S. Taylor — 2009-07-09

Objective: To report a novel mutation found in a family with hand-foot-genital syndrome (HFGS). To characterize the genetic basis of true HFGS versus presence of non-HFGS-related uterovaginal septa.Design: Case-control study.Setting: Academic medical center.Patient(s): The HFGS patients and family members; women with uterine or uterovaginal septa without other sequelae of HFGS.Intervention(s): Sequence analysis of HOXA13 in members of a family with HFGS (3 affected, 1 unaffected); sequence analysis of HOXA13 in biopsy samples obtained from 17 non-HFGS patients with idiopathic uterine or uterovaginal septa and in 11 normal controls.Main Outcome Measure(s): Presence or absence of mutations of HOXA13.Result(s): Affected members of a family with HFGS showed a novel expansion of the third polyalanine tract of HOXA13, inserting 10 alanines in-frame. None of the patients with idiopathic uterovaginal septa displayed mutations of HOXA13.Conclusion(s): The cause of uterovaginal septa without hand and foot symptoms differs from true HFGS. When patients present with septa, it is not necessary to subject them to roentgenograms of the distal limbs or to sequence analysis of HOXA13 unless they show clear signs of the other sequelae characteristic of true HFGS.

Perspectives of couples with high risk of transmitting genetic disorders

2009-10-07

Objective: To investigate the preference for preimplantation genetic diagnosis (PGD) as an alternative to prenatal diagnosis (PND) in a large group of couples representing a wide array of genetic disorders. We also investigated the couple's familiarity with PGD and presented time trade-off scenarios for PGD versus PND, as PGD treatment is regularly accompanied by waiting lists.Design: Questionnaire study.Setting: Patient organizations representing genetic disorders.Patient(s): A total of 210 couples carrying genetic disorders.Main Outcome Measure(s): Preference for PGD or PND and familiarity with PGD in carrier couples.Result(s): Fifteen organizations representing 38 genetic disorders agreed to participate. Nine hundred eighty-three couples responded. In total 210 couples were in their reproductive years (women 18–40 years) and had a desire to conceive. Ninety couples (42%) had never heard of PGD. After they were informed, 127 couples (60%) wanted to have diagnostic testing (PND or PGD) performed. Ninety-four (74%) of these couples preferred testing with PGD. When no waiting list was used 102 couples (80%) preferred PGD. With a 2-year waiting list for PGD, 58 couples (46%) would opt for PGD.Conclusion(s): Many carrier couples are unaware of the existence of PGD. When informed, most couples prefer PGD more than PND. The preference for PGD decreases with longer waiting lists.

Association study of AMH and AMHRII polymorphisms with unexplained infertility

2009-06-19

Objective: To investigate the association of AMH and AMHRII polymorphisms with reproductive abilities in a sample of women with idiopathic infertility.Design: Case-control study.Setting: University Department of Obstetrics and Gynecology, and University Unit of Clinical Genetics.Patient(s): 76 women with idiopathic sterility and 100 fertile women as controls.Intervention(s): Genotyping was performed by high-resolution melt analysis.Main Outcome Measure(s): Genotype distribution and allele frequency of AMH and AMHRII polymorphisms. Reconstruction of haplotype alleles to evaluate the linkage disequilibrium between single nucleotide polymorphisms.Result(s): Allele frequencies of –482 A>G, IVS 5–6 C>T, IVS 10+77 A>G, 146T>G polymorphisms are statistically significantly different in infertile patients compared with controls.Conclusion(s): Genetic variants of AMH and AMHRII genes seem to be associated with infertility, suggesting a role in the pathophysiology of normo-estrogenic and normo-ovulatory infertility. A clearer understanding of their function in ovarian physiology may help clinicians to find a role for antimüllerian hormone measurement in the field of reproductive medicine.

Asian women are less likely to express interest in infertility research

2009-10-05

Objectives: To assess the differences among racial and ethnic groups in their willingness to participate in medical infertility research. We further explored these differences within racial and ethnic subcategories to gain a broader understanding of minority patients' willingness to participate in infertility research.Design: Cross-sectional study.Setting: University fertility center.Patient(s): One thousand forty-nine women presenting for reproductive care.Intervention(s): None.Main Outcome Measure(s): Willingness to be contacted for recruitment to ongoing research.Result(s): Asians were less likely than non-Hispanic Whites to express willingness to be contacted regarding research (odds ratio 0.44, 95% confidence interval 0.33; 0.57), as were Middle Eastern women. Decreased willingness was seen in all Asian subcategories except Vietnamese. Women born outside the United States were less likely to consent to be contacted than those born in the United States.Conclusion(s): Asian and Middle Eastern patients are less likely than non-Hispanic Whites to express interest in research participation in the infertility clinic setting. Strategies to target these women for research recruitment are necessary to achieve parity in both research participation and assisted reproductive technology outcomes.

Determinants of patients' experiences and satisfaction with fertility care

2009-09-03

Objective: To assess determinants of patients' experiences and satisfaction with fertility care.Design: Cross-sectional questionnaire study.Setting: Sixteen fertility clinics in The Netherlands.Patient(s): A total of 1,499 infertile women in The Netherlands who visited a participating clinic in April–June 2005 for diagnostics or treatment.Main Outcome Measures: Patients experiences and satisfaction with several aspects of fertility care, and the patient and clinic characteristics that are determinants of those two concepts.Result(s): In general, patients' satisfaction with care was high (94%). Waiting times, information provision and emotional support were experienced the least positive aspects of care. Determinants of all care aspects were found to be significant at four different domains: three at patient level, i.e., demographic characteristics, type of received treatment and both general and mental health status, and one at clinic level, i.e., organization of care.Conclusion(s): This study provides an increased understanding of the determinants of patients' experiences and satisfaction with fertility care. This enables professionals to tailor their care to specific subgroups of patients and adjust their organization of fertility care where needed. Moreover, the study underlines the need to investigate whether case-mix correction is necessary whenever interpreting patient-surveys on care experiences, because both the patient's and the clinic's characteristics can influence the way that health care delivery is experienced. Demographic background of this regional patient sample was rather homogeneous, which should be taken into account when interpreting results.

Double versus single intrauterine insemination for unexplained infertility: a meta-analysis of randomized trials

Nikolaos P. Polyzos, Spyridon Tzioras, Davide Mauri, Athina Tatsioni — 2009-08-10

Objective: To investigate the effect of double versus single intrauterine insemination (IUI) per treatment cycle in women with unexplained infertility.Design: Meta-analysis of randomized controlled trials.Main Outcome Measure(s): Clinical pregnancy rates per couple.Intervention(s): Electronic searches of the Cochrane Central Trials Registry and Medline without year and language restriction through March 2009; hand searching of the abstract books of the European Society of Human Reproduction and Embryology and American Society for Reproductive Medicine annual meetings (2001–2008).Result(s): Six randomized trials, involving 829 women, were included in the analysis. Fifty-four (13.6%) clinical pregnancies were recorded for treatment with double IUI and 62 (14.4%) for treatment with single IUI. There was no significant difference between the single and double IUI groups in the probability for clinical pregnancy (odds ratio, 0.92; 95% confidence interval, 0.58–1.45; P=0.715).Conclusion(s): Double IUI offers no clear benefit in the overall clinical pregnancy rate in couples with unexplained infertility.

Comparison of the effectiveness of single versus double intrauterine insemination with three different timing regimens

2009-09-28

Objective: To compare double insemination with two different single insemination regimens.Design: Prospective study.Setting: Tertiary education and research hospital.Patient(s): Four hundred and fifty patients with unexplained infertility, male factor, and ovulatory dysfunction underwent controlled ovarian hyperstimulation with gonadotropin.Intervention(s): The patients were divided randomly into three groups: patients in group 1 underwent a single preovulatory intrauterine insemination (IUI) performed 24 hours after hCG administration. Patients in group 2 underwent two IUIs performed 12 and 36 hours after hCG administration. Patients in group 3 underwent a single periovulatory IUI performed 36 hours after hCG administration.Main Outcome Measure(s): Pregnancy rate.Result(s): The total pregnancy rate per patient was 14.2 % (64 pregnancies in 450 patients). Group 1 had 17 pregnancies (11.3%), while groups 2 and 3 had 21 (14.0%) and 26 (17.2%) pregnancies, respectively. The difference between the three groups in regard to pregnancy rates was statistically not significant.Conclusion(s): Despite the 36th hour being the preferred timing for IUI, there was no difference regarding pregnancy rates between single 24th hour and double 12th- and 36th-hour inseminations. This finding suggests that the 24th-hour IUI might be preferred in demanding situations.

Defective endometrial prostaglandin synthesis identified in patients with repeated implantation failure undergoing in vitro fertilization

Hanna Achache, Avi Tsafrir, Diana Prus, Reuven Reich, Ariel Revel — 2009-10-07

Objective: To define the role of prostaglandins (PG) in the endometrium of patients with repeated failure of embryo implantation. Prostaglandins are produced after the sequential oxidation of arachidonic acid by cyclooxygenases (COX-1 and COX-2) and terminal PG synthases.Design: Case-control study.Setting: In vitro fertilization unit at a university hospital.Patient(s): Thirty-four women, comprising of 19 patients with repeated IVF failure and 15 controls with proven fertility.Intervention(s): Endometrial expression levels of the enzymes responsible for the PG synthesis were compared between the two groups.Main Outcome Measure(s): Cytosolic phospholipase A2 (cPLA2α) expression and activity were assessed by Western blot. Expression of cyclooxygenase-2, secretory phospholipase A2 group IIA, V, and IB (sPLA2-IIA, sPLA2-V, sPLA2-IB), glypican-1, PG E synthase, PG E receptors, and lysophosphatidic acid receptor 3 (LPA3) was measured by real-time polymerase chain reaction (PCR). Localization of COX-2, sPLA2-IIA, and LPA3 within the secretory endometrium was detected by immunohistochemistry.Result(s): Patients displaying recurrent implantation failure expressed reduced levels of cPLA2α and COX-2 compared with controls. In response to this deficiency, sPLA2-IIA was found to be overexpressed. Interestingly, LPA3, which is known to converge on the cPLA2-arachidonic acid-COX-PG signaling pathway, was also decreased in these patients.Conclusion(s): Prostaglandin synthesis appears to be disrupted in patients with repeated IVF failure compared with fertile controls. We therefore suggest that reduced PG synthesis in the human endometrium may lead to poor endometrial receptivity.

Serum oxidizability and antioxidant status in patients undergoing in vitro fertilization

2009-06-22

Objective: To evaluate the serum oxidizability and antioxidant status in women undergoing an in vitro fertilization (IVF) cycle and to assess the possible relationship of the oxidizability indexes with the pregnancy rate.Design: Prospective, longitudinal study.Setting: Public university and public university hospital.Patient(s): Systematically recruited cohort of 125 women undergoing either IVF or intracytoplasmic sperm injection (ICSI).Intervention(s): Serum samples were collected before the beginning of the use of gonadotropins (basal) and the day of human chorionic gonadotropin (hCG) administration (final) during an IVF cycle.Main Outcome Measure(s): The Cu2+-induced serum oxidation in terms of the oxidation rate in the lag (Vlag) and propagation (Vmax) phases and the time at which the oxidation rate is maximal (tmax), and measurements of serum total antioxidant activity (TAA), tocopherol, hydrophilic antioxidants, malondialdehyde, and nitric oxide.Result(s): Albumin, urate, bilirubin, α-tocopherol and γ-tocopherol, TAA, and tmax statistically significantly decreased after the IVF cycle. Conception cycles were associated with a serum more prone to oxidation compared with nonconception cycles. In multivariate logistic regression analysis, the difference (final-basal) of the oxidation index Vlag (OR 1.394) and the body mass index (OR 0.785) were independent predictors of pregnancy.Conclusion(s): Treatment with IVF induces the production of reactive oxygen species (ROS), which is reflected in a serum less protected against oxidation. The results also suggest a role for ROS in the occurrence of conception in IVF.

Factors affecting success rates in two concurrent clinical IVF trials: an examination of potential explanations for the difference in pregnancy rates between the United States and Europe

2009-10-07

Objective: To compare a US clinical trial of gonadotropin therapy for IVF with a similar European trial to determine what factors may explain the higher clinical pregnancy rate in the US trial.Design: Comparison of baseline, treatment, and outcome variables in the United States (US) and European trials.Setting: IVF practices in the US (n=4) and Europe (n=6).Patient(s): 297 women undergoing IVF.Intervention(s): None.Main Outcome Measure(s): Clinical pregnancy rate.Result(s): Clinical pregnancy rates were 43.4% in the US compared with 29.7% in Europe (p=0.016), with a live birth rate of 38.2% versus 27.6% (p=0.064). This difference in clinical pregnancy rate could not be explained by differences in the US versus Europe for number of embryos transferred (2.3 vs. 2.6) or female age (34.6 vs. 30.4). Although the starting dose of gonadotropin was higher in the US trial compared with the European trial (300 versus 225 IU), the total dose of gonadotropin was only slightly higher in the US. In multiple logistic regression analysis of 81 pretransfer variables on clinical pregnancy, the only two found to be significant predictors of outcome were baseline endometrial thickness following down-regulation and number of days of gonadotropin treatment.Conclusion(s): This study suggests the possibility that US pregnancy rates may be higher in part because of differences in down-regulation or gonadotropin dosing. Other factors not assessed in these studies or in national datasets likely also contribute to the difference in pregnancy rates.

Multivariate analysis of the association between oocyte donor characteristics, including basal follicle stimulating hormone (FSH) and age, and IVF cycle outcomes

Sara E. Barton, Stacey A. Missmer, Rachel K. Ashby, Elizabeth S. Ginsburg — 2009-10-12

Objective: To determine whether oocyte donor FSH and age are independently associated IVF cycle success.Design: Retrospective cohort study.Setting: University hospital-based IVF clinic.Patient(s): Three hundred twelve donor/recipient pairs undergoing oocyte donation IVF.Main Outcome Measure(s): Number of mature oocytes and embryos, clinical pregnancy, and live birth rates.Result(s): Donors' basal FSH levels were not associated with IVF cycle outcomes. However, for every year increase in donor age, the number of mature oocytes decreased by 0.39 and the number of embryos decreased by 0.25 resulting in 1 less embryo for each 4-year increase in age, even in young donors. For every 100 pg/mL increase in estradiol on the day of hCG administration, the number of mature oocytes increased by 0.49 and the number of embryos increased by 0.36. For each additional 75 IU of gonadotropin used during stimulation, the likelihood of pregnancy and live birth decreased by 3.5%.Conclusion(s): Donor oocyte IVF cycle outcomes were not associated with donor basal FSH. However, donor age and estradiol level on the day of hCG administration were significantly associated with numbers of mature oocytes and embryos obtained, and the amount of gonadotropin used in the stimulation was significantly associated with the likelihood of pregnancy and live birth.

Single and multidose pharmacokinetic study of a vaginal micronized progesterone insert (Endometrin) compared with vaginal gel in healthy reproductive-aged female subjects

2009-07-15

Objective: To determine pharmacokinetic profiles of two times a day and three times a day dosage regimens of Endometrin, a micronized progesterone vaginal insert for luteal support in assisted reproductive technology, compared with a gel.Design: A single-center, randomized, open-label, single-day, and multiple-day (5 days) parallel design pharmacokinetic study.Setting: University clinical research unit.Patient(s): Three groups of six healthy subjects, ages 18 to 40 years.Intervention(s): Endometrin vaginal inserts two times a day or three times a day, or gel daily.Main Outcome Measure(s): Pharmacokinetic profiles.Result(s): Progesterone serum concentrations increased rapidly following administration of Endometrin vaginal insert, producing higher peak concentrations (Cmax) and clearing faster than gel. On the single day of dosing, mean Cmax was 17.0 ± 2.7 ng/mL in the two times a day group, 19.8 ± 2.9 ng/mL in the three times a day group, and 6.82 ± 1.69 ng/mL in the gel group. Endometrin treatments reached steady state within the first 2 days (24–36 hours), much more rapidly than the gel, which had not reached steady state by 5 days. At 5 days, the Endometrin treatments produced sustained progesterone concentrations exceeding 10 mg/mL across 24 hours.Conclusions: Endometrin vaginal inserts reached higher Cmax, produced greater systemic exposure (area under the curve 0–24), achieved steady state more rapidly, and cleared more rapidly after termination of therapy than the comparator.

Mechanically expanding the zona pellucida of human frozen thawed embryos: a new method of assisted hatching

Cong Fang, Tao Li, Ben-Yu Miao, Guang-Lun Zhuang, Canquan Zhou — 2009-09-28

Objective: To determine whether a new assisted hatching (AH) method increases the implantation and clinical pregnancy rates of frozen–thawed day-3 (D3) embryos.Design: Prospective study.Setting: A university hospital in vitro fertilization (IVF) program.Patient(s): Patients who had their first IVF/intracytoplasmic sperm injection (ICSI) cycles between June 1, 2006, and December 31, 2008, with fresh IVF–embryo transfer failures or without fresh embryo transfer.Intervention(s): The couples were randomized into thawed embryo transfer after AH versus no AH. In the AH group, the zona pellucida (ZP) of D3 frozen–thawed embryos was expanded by injected hydrostatic pressure after thawing. In the control group, embryos were pierced by ICSI needles without expanding the ZP.Main Outcome Measure(s): Clinical pregnancy and implantation rates.Result(s): The morphologic features of the blastomeres were carefully monitored and recorded. In the AH group, 244 embryos were thawed, and 178 (73.0%) survived; in the control group, 259 embryos were thawed, and 190 (73.4%) survived. Despite the transfer of a similar number of embryos, the AH group resulted in statistically significantly higher implantation and clinical pregnancy rates compared with the no AH group.Conclusion(s): Mechanically expanding the ZP of frozen–thawed D3 embryos with injected hydrostatic pressure after thawing increases the implantation rate compared with control embryos.

Factors affecting thawed oocyte viability suggest a customized policy of embryo transfer

2009-08-14

Objective: To identify factors that might affect the clinical outcome of oocyte slow freezing.Design: Retrospective study.Setting: Reproductive Medicine Unit, Italian Society for the Study of Reproductive Medicine, Bologna, Italy.Patient(s): Patients with spare metaphase II cryopreserved oocytes performing 371 thawing cycles.Intervention(s): Oocytes were cryopreserved by slow freezing <40 hours after hCG administration (group A) and ≥40 hours after hCG administration (group B). Thawed oocytes were inseminated by intracytoplasmic sperm injection.Main Outcome Measure(s): Clinical pregnancy, implantation, abortion, and delivery rates.Result(s): Clinical pregnancy rate per thawed cycle (PR) and implantation rate (IR) were significantly higher in group A compared with group B both in young (PR: 25% vs. 9.6%; IR: 18.9% vs. 8.8%) and in older patients (PR: 25% vs. 10.1%; IR: 17.5% vs. 6.7%). In the young patient subgroup, clinical pregnancy and implantation rates with three transferred embryos were higher in group A vs. group B (PR: 72.7% vs. 25%, and IR: 36.4% vs. 12.5%, respectively). This difference was not found in the subgroup of older patients.Conclusion(s): The timing at which oocyte cryopreservation is performed and the number of transferred embryos play a key role in the clinical outcome. The suggested cut-off time for cryopreservation is between 39 and 40 hours after hCG administration.

Replete vitamin D stores predict reproductive success following in vitro fertilization

2009-07-08

Objective: To determine whether 25OH-D levels in the follicular fluid (FF) of infertile women undergoing IVF demonstrate a relationship with IVF cycle parameters and outcome, hypothesizing that levels of 25OH-D in body fluids are reflective of vitamin repletion status.Design: Prospective cohort study.Setting: Academic tertiary care center.Patient(s): Eighty-four infertile women undergoing IVF.Intervention(s): Follicular fluid from follicles ≥14mm; serum (n = 10) and FF levels of 25OH-D.Main Outcome Measure(s): Clinical pregnancy (CP), defined as evidence of intrauterine gestation sac on ultrasound, following IVF; IVF cycle parameters.Result(s): Serum and FF levels of 25OH-D were highly correlated (r = 0.94). In a predominantly Caucasian population (66%), significantly lower FF 25OH-D levels were noted in Black versus non-Black patients. Significant inverse correlations were seen between FF 25OH-D levels and body mass index (r = –0.25). Significantly higher CP and implantation rates were observed across tertiles of FF25OH-D; patients achieving CP following IVF (n = 26) exhibited significantly higher FF levels of 25OH-D. Multivariable logistic regression analysis confirmed FF 25OH-D levels as an independent predictor to success of an IVF cycle; adjusting for age, body mass index, ethnicity, and number of embryos transferred, each ng/mL increase in FF 25OH-D increased the likelihood for achieving CP by 6%.Conclusion(s): Our findings that women with higher vitamin D level in their serum and FF are significantly more likely to achieve CP following IVF–embryo transfer are novel. A potential for benefit of vitamin D supplementation on treatment success in infertile patients undergoing IVF is suggested and merits further investigation.

Infant outcome of 957 singletons born after frozen embryo replacement: The Danish National Cohort Study 1995–2006

2009-07-31

Objective: To examine infant outcome of singletons born after cryopreservation of embryos (Cryo).Design: National population-based controlled follow-up study.Setting: Denmark, 1995–2007.Patient(s): The study population was 957 Cryo singletons (Cryo-IVF, n = 660; Cryo-ICSI, n = 244; Cryo-IVF/-ICSI, n = 53). The first control group was all singletons born after fresh IVF or intracytoplasmic sperm injection (ICSI) during the same period (IVF, n = 6904; ICSI, n = 3425). The second control group comprised a random sample of non–assisted reproductive technology (ART) singletons (n = 4800).Intervention(s): All observations were obtained from national registers.Main Outcome Measure(s): Low birth weight (LBW; <2500 g), preterm birth (PTB; < 37 weeks), congenital malformations, mortality, and morbidity.Result(s): Birth weight was higher in Cryo (mean = 3578 g, SD = 625) versus fresh (mean = 3373 g, SD = 648) and in Cryo versus non-ART (mean = 3537 g, SD = 572), and this was also the case for first birth only. Lower adjusted risk of LBW (odds ratio [OR] = 0.63; 95% confidence interval [CI], 0.45–0.87) and PTB (OR = 0.70; 95% CI, 0.53–0.92) was observed in Cryo versus fresh. Similar LBW and PTB rates were observed when comparing Cryo with non-ART, but the perinatal mortality rate was doubled in Cryo (1.6%) compared with non-ART (0.8%) singletons, and the adjusted risks of very preterm birth (<34 weeks) and neonatal admittance were also significantly increased. No significant differences in the prevalence rates of birth defects, neurological sequelae, malignancies, and imprinting-related diseases were observed between the Cryo and the two control groups. However higher malformation and cerebral palsy rates were observed in the total Fresh vs. non-ART group.Conclusion(s): Cryo singletons have better neonatal outcome than offspring after fresh ET but poorer compared with non-ART singletons.

Fertilization rate is an independent predictor of implantation rate

2009-06-29

Objective: To determine whether fertilization rate serves as a biological assay, reflects oocyte quality, and may be used to help predict patient implantation rate.Design: Retrospective cohort study.Setting: Academic center.Patient(s): Couples undergoing 3603 in vitro fertilization (IVF) cycles from 2001 to 2007.Intervention(s): None.Main Outcome Measure(s): We compared the implantation rate among cycles with high versus low fertilization rate. Univariate analyses were performed to determine the association of implantation rate with potential confounding variables: age, day-3 follicle-stimulating hormone level, day-3 estradiol level, antral follicle count, oocyte number, cycle attempts, embryo grading, and number of embryos transferred. Multivariate analysis was then performed to determine whether the fertilization rate remained an independent predictor.Result(s): Cutoffs for fertilization rate were 50% for intracytoplasmic sperm injection (ICSI) and 75% for conventional insemination. Higher ICSI fertilization was statistically significantly associated with the implantation rate (25.2% vs. 17.8 %). After adjusting for variables associated with implantation rate, fertilization rate for ICSI remained a strong independent predictor of implantation. Higher conventional insemination fertilization was statistically significantly associated with implantation (32.1% vs. 25.7%) and remained a statistically significant predictor after adjustment.Conclusion(s): Fertilization is a strong, independent predictor of implantation rate and may be useful in modeling to guide decision making for the number of embryos to transfer.

Calculating cumulative live-birth rates from linked cycles of assisted reproductive technology (ART): data from the Massachusetts SART CORS

2009-07-10

Objective: To determine the feasibility of linking assisted reproductive technology (ART) cycles for individual women to compare per-cycle and cumulative live-birth rates.Design: Historical cohort study.Setting: Clinic-based data.Patient(s): A total of 27,906 ART cycles with residency or treatment in Massachusetts during 2004–2006 and reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS) on-line database.Intervention(s): None.Main Outcome Measure(s): Per-cycle and cumulative live-birth rates.Result(s): Linkage of cycles up to and including the first live-birth delivery revealed 14,265 women who averaged 1.9 ± 1.2 SD cycles (range 1–11). These cycles yielded 9,452 pregnancies resulting in 7,675 live-birth deliveries. From cycle 1 to cycle 4, the cumulative live-birth rate for all patients increased from 30.4% to 43.3%, 49.1%, and 51.9%, respectively, and plateaued thereafter at about 53%. The cumulative live-birth rate after three cycles using donor oocytes was ∼60% for women aged <43 years and >50% for women ≥43 years; for autologous oocytes it was 60.1% for ages <35 years and declined steadily to 8.5% for ages ≥43 years.Conclusion(s): The results demonstrate the feasibility of linking ART cycles for individual women from SART CORS to characterize cumulative live-birth rates.

Impact of embryo replacement depth on in vitro fertilization and embryo transfer outcomes

2009-12-30

Objective: To investigate the impact of embryo replacement depth on IVF and embryo transfer outcomes.Design: Retrospective analysis (May 2005 to November 2008) of 5,055 ultrasound-guided embryo transfers belonging to 3,930 infertile couples. The distance between the fundal endometrial surface and the catheter tip was measured and accordingly, patients were divided into five groups.Setting: Anatolia IVF Center, Ankara, Turkey.Patient(s): All patients enrolled in the IVF program undergoing embryo transfer.Intervention(s): No patient received any additional procedure or intervention.Main Outcome Measure(s): Clinical pregnancy rate (PR) and ongoing PR.Result(s): Mean total number of embryos transferred in groups 4 and 5 were significantly higher than in groups 2 and 3. Analysis of PRs and outcome of gestations in the five groups studied yielded similar PRs in all groups except for group 1.Conclusion(s): Pregnancy rates and ongoing PRs are higher if the embryos are replaced at a distance >10 mm from the fundal endometrial surface. In addition because significantly more embryos were replaced in cycles where the transfers occurred at a distance of >20 mm, a distance >10 mm to <20 mm seems to be the best site for embryo transfer to achieve higher PRs.

What do consistently high-performing in vitro fertilization programs in the U.S. do?

Bradley J. Van Voorhis, Mika Thomas, Eric S. Surrey, Amy Sparks — 2010-08-02

Objective: To identify common clinical and laboratory practices among consistently high-performing IVF programs.Design: Questionnaire study of selected IVF programs.Setting: Academic and private practice IVF programs.Patient(s): Ten of 12 programs identified as having consistently high singleton delivery rates per cycle.Intervention(s): None.Main Outcome Measure(s): Common clinical practices.Result(s): Common clinical practices identified among these programs included testing all patients for ovarian reserve, endometrial defects, and hydrosalpinges; use of a mixed LH and FSH stimulation protocol with step-down dosing; and use of ultrasound guidance for ET. Common laboratory practices included selective use of intracytoplasmic sperm injection, group culture of embryos in microdrops, and use of blastocyst ET in selected cases. Common laboratory features included good air quality using filtration and heated stages for oocyte and embryo work.Conclusion(s): Although a number of factors were identified in this best-practices questionnaire, programs often differed in many aspects of care. However, high-performing programs cited experience of physicians, embryologists, and staff members as well as consistency of approach, attention to detail, and good communication as being vital to excellent outcomes.

Early and short follicular gonadotropin-releasing hormone antagonist supplementation improves the meiotic status and competence of retrieved oocytes in in vitro fertilization–embryo transfer cycles

2009-10-01

Objective: To investigate whether early and short follicular administration of GnRH antagonist using the flexible protocol has the potential to improve IVF-ET clinical results.Design: Prospective, controlled, randomized study.Setting: University-affiliated assisted reproductive technology unit.Patient(s): Fifty-three consecutive infertile women were enrolled to the study and control groups.Intervention(s): Both groups were treated with recombinant FSH and the flexible GnRH antagonist protocol. Women in the study group were additionally supplemented with three injections of GnRH antagonist (0.25 mg/d on days 1, 2, and 3 of the menstrual cycle).Main Outcome Measure(s): Hormonal milieu, oocyte meiotic status, competence for normal fertilization, cleavage, and clinical pregnancy rate.Result(s): Both groups had comparable baseline characteristics. The duration of recombinant FSH treatment was significantly longer in the study group as compared with the control group (10.9 ± 3.1 and 9.7 ± 1.3 days, respectively). The number of follicles ≥14 mm and E2 level on the day of hCG administration, number of retrieved oocytes, and endometrial thickness were similar between the two groups. However, the fertilization rate was significantly higher in the study as compared with the control group (85% ± 16% and 69% ± 24%, respectively). Moreover, the cumulative rate of mature first polar body oocytes was significantly higher in the study group as compared with the control group (93% and 85%, respectively). Concomitantly, day-3 FSH and LH levels after initiation of treatment were significantly lower in the study as compared with the control group (6.1 ± 2.4 mIU/mL vs. 7.2 ± 1.9 mIU/mL and 2.4 ± 1.6 mIU/mL vs. 5.6 ± 2.7 mIU/mL, respectively).Conclusion(s): Early and short follicular GnRH antagonist supplementation using flexible GnRH antagonist treatment improves the meiotic status and competence of retrieved oocytes. It seems that early and short pituitary shutdown has the potential to improve clinical results in IVF-ET GnRH antagonist cycles.

Healthy overweight male partners of subfertile couples should not worry about their semen quality

Floor H. Duits, Madelon van Wely, Fulco van der Veen, Judith Gianotten — 2009-07-15

Objective: To study the effect of body mass index (BMI) on semen quality in a cohort of male partners in subfertile couples.Design: Prospective cohort study.Setting: A fertility center based in an academic hospital.Patient(s): Between January 2000 and January 2007, 1466 men visiting the Centre for Reproductive Medicine as part of a subfertile couple.Intervention(s): None.Main Outcome Measure(s): Semen volume (in mL), semen concentration (in millions per mL), percentage of motile spermatozoa, percentage of spermatozoa with normal forms, total sperm count (in millions), and total motile sperm count (in millions).Result(s): After exclusion of men without data on BMI, the data of 1401 men could be analyzed. The group of men with a BMI lower than 20 kg/m2, with a BMI between 25 and 30 kg/m2, and with a BMI >30 kg/m2 had a lower semen volume compared with the group with a BMI between 20 and 25 kg/m2. Other semen parameters were not statistically significantly different. Multivariable analysis (generalized linear model), correcting for confounders, showed no statistically significant association between BMI and semen parameters, including semen volume.Conclusion(s): Semen quality was not statistically significantly affected by BMI in a cohort of male partners in subfertile couples.

The transcriptome of spermatozoa used in homologous intrauterine insemination varies considerably between samples that achieve pregnancy and those that do not

2009-09-30

Objective: To differentiate transcripts' expression in the sperm from patients who achieved pregnancy in their first IUI cycle from those who did not. Basic sperm analysis is limited to forecasting pregnancies by means of assisted reproduction. New assays, such as microarray analysis, are potential predictive tools for this purpose.Design: Nested case-control study.Setting: University-affiliated private setting.Patient(s): Twenty sperm samples were obtained from infertile males undergoing their first IUI cycle with healthy partners. Sperm samples with which pregnancy was achieved (P; n = 10) and those with which it was not achieved (NP; n = 10) were identified and their respective messenger RNA expression profiles were compared.Intervention(s): None.Main Outcome Measure(s): Using microarrays, global genome expression was compared in pooled samples from each group. Results were evaluated to detect differentially expressed transcripts (TDEs; FC>2; P<0.05) and to identify those transcripts that were expressed in only one of the groups (exclusive transcripts [ETs]).Result(s): In group P, 756 TDEs presented increased expression, whereas 194 in group NP were found to be overexpressed. Furthermore, we found 741 ETs that were expressed only in group P and 976 that were expressed only in group NP.Conclusion(s): Results reveal profound differences between expression profiles of sperm samples that impregnate successfully and those that do not. These differences might improve the predictive power of sperm evaluation to estimate IUI success by complementing the basic sperm analysis.

Impact of chemotherapeutics and advanced testicular cancer or Hodgkin lymphoma on sperm deoxyribonucleic acid integrity

Cristian O'Flaherty, Barbara F. Hales, Peter Chan, Bernard Robaire — 2009-07-09

Objective: To determine the impact of combination chemotherapy on the quality of newly generated spermatozoa from patients with advanced testicular cancer and patients with Hodgkin lymphoma (HL).Design: Prospective longitudinal study.Setting: Academic facility.Patient(s): Patients with newly diagnosed metastatic testicular cancer and with HL that required chemotherapy were compared with age-matched healthy community volunteers.Intervention(s): None.Main Outcome Measure(s): Semen parameters, hormone levels, testis volume, and presence of sperm DNA strand breaks in patients with cancer and in healthy community volunteers were compared before and after the patients' chemotherapy at 6, 12, 18, and 24 months.Result(s): Before chemotherapy, both cancer groups had poorer semen quality compared with community volunteers. Among patients with testicular cancer and HL, 67% and 60%, respectively, had <5 × 106 sperm/mL at 6 months after chemotherapy. At 24 months, 60% and 57% of patients with testicular cancer and HL, respectively, had normal sperm concentrations. Level of FSH was significantly higher in the cancer group compared with community volunteers at 6 to 12 months after chemotherapy. Before chemotherapy, sperm DNA damage was higher in the cancer group than in community volunteers; this damage was increased further at 6 months and remained elevated 24 months after treatment.Conclusion(s): Sperm generated after chemotherapy maintain a significant degree of chromatin damage. Therefore, survivors of testicular cancer and HL are at risk of having abnormal reproductive outcome. Proper counseling to these patients on reproductive risks and fertility preservation before chemotherapy is recommended.

Impact of different patterns of sperm chromosomal abnormalities on the chromosomal constitution of preimplantation embryos

2009-07-15

Objective: To evaluate the effect of sperm chromosome abnormalities—disomy for sex chromosomes and diploidy—in the chromosomal constitution of preimplantation embryos.Design: Retrospective cohort study.Setting: Infertility clinic.Patient(s): Three groups: 46,XY infertile men with increased incidence of sex chromosome disomy in sperm; 46,XY infertile men with increased diploidy rates in sperm; 47,XYY infertile men with increased sex chromosome disomy and diploidy rates in sperm.Intervention(s): Sperm collection for fluorescence in situ hybridization analysis. Embryo biopsy for preimplantation genetic screening.Main Outcome Measure(s): Frequencies of numerical abnormalities in sperm for chromosomes 13, 18, 21, X, and Y, and in embryos for chromosomes 13, 16, 18, 21, 22, X, and Y.Result(s): A significant increase of chromosomally abnormal and mosaic embryos was observed in the three study groups compared with controls. Those sperm samples with increased sex chromosome disomy rates produced significantly higher percentages of aneuploid embryos, with a threefold increase for sex chromosomes. Sperm samples with increased diploidy rates were mainly associated to the production of triploid embryos.Conclusion(s): A strong correlation between sperm and embryo chromosomal constitution has been shown in infertile men with 46,XY and 47,XYY karyotypes.

Discontinuation of hormone therapy in the French GAZEL cohort 1990–2006

2009-09-11

Objective: To analyze changes in hormone therapy (HT) use after the publication of the Women's Health Initiative (WHI) results, in a country (France) where HT is different from that assessed in the WHI.Design: Longitudinal study.Setting: Women in the GAZEL cohort of employees of the French national power company.Participant(s): One thousand six hundred five postmenopausal women ever-users of HT.Intervention(s): None.Main Outcome Measure(s): Discontinuation of HT.Result(s): Rates of discontinuation were higher after 2002: 65% of users who began HT in 1998 were still using it after 5 years. In contrast, >90% of those who began before 1994 were still using it after 5 years. Discontinuation was associated with women's social and medical characteristics and with factors related to side effects and expectations concerning HT. After adjustment for these factors, women were twice as likely to stop HT after publication of the WHI.Conclusion(s): Even in France, publication of the WHI has led to a decline in HT use.

The pathophysiology of ovarian hyperstimulation syndrome: an unrecognized compartment syndrome

2009-10-15

Objective: To compare and contrast the pathophysiology of ovarian hyperstimualtion syndrome (OHSS) with known syndromes of increased intraabdominal pressure (IAP), and to explore the relationship of increased IAP with symptom severity in OHSS.Design: Literature review.Main Outcome Measure(s): Correlation of OHSS symptoms with IAP; effects of paracentesis on IAP in patients with OHSS.Setting: Academic Research Institution.Intervention(s): None.Result(s): OHSS involves a rapid accumulation of volume (from 1.5–17 liters) in the peritoneal cavity that can lead to organ dysfunction, including respiratory impairment and oliguria. In published reports of 20 moderate-to-severe OHSS patients in whom IAP was measured, IAP was found to be elevated to a pathologic range. The increased IAP indicates that OHSS may be considered a compartment syndrome and meets criteria for abdominal compartment syndrome in advanced cases. For this reason, management of OHSS should include reduction of pressure by paracentesis to avoid morbidity and syndrome progression. In addition, measurement of IAP may help to classify the stage of OHSS.Conclusion(s): IAP was found to be elevated in the few cases of OHSS in which it was measured, substantiating the conclusion that OHSS may be considered a compartment syndrome. An understanding of the pathophysiology of increased intrabdominal pressure is useful in the management of OHSS.

Factors associated with ovarian hyperstimulation syndrome (OHSS) and its effect on assisted reproductive technology (ART) treatment and outcome

2009-07-09

Objective: To evaluate factors associated with ovarian hyperstimulation syndrome (OHSS) and its effect on assisted reproductive technology (ART) treatment and outcome.Design: Historic cohort study.Setting: Clinic-based data.Patient(s): The population included 214,219 ART cycles performed during 2004 to 2006 and reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System Online database. The study population was limited to cycles of autologous, fresh embryo transfers to women without any treatment complications (212,041), and those developing moderate (1,523) or severe (655) OHSS.Intervention(s): None.Main Outcome Measure(s): Risk factors for developing OHSS, and its effect on achieving a pregnancy and live birth, as adjusted odds ratios.Result(s): Compared with white women, the risk of developing OHSS was increased for Black women (any OHSS, 1.88; severe OHSS, 2.93) and decreased for Hispanic women (any OHSS, 0.79). Ovarian hyperstimulation syndrome was associated with ovulation disorders (2.01), tubal factors (1.24), and unexplained factors (1.36). Ovarian hyperstimulation syndrome increased the odds of achieving a pregnancy (1.98 with any OHSS, 2.68 with severe), a live birth (any OHSS, 1.86), and a multiple live birth (1.58 with any OHSS, 1.86 with severe). The presence of any OHSS increased the risk of an adverse pregnancy outcome (stillbirth, low birthweight, or preterm birth) by 26% and low birthweight among singletons by 40%.Conclusion(s): Ovarian hyperstimulation syndrome is associated with a higher likelihood of pregnancy, and multiple gestations, but also greater risks for adverse pregnancy outcomes.

Letrozole versus combined metformin and clomiphene citrate for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial

Hatem Abu Hashim, Tarek Shokeir, Ahmed Badawy — 2009-09-03

Objective: To compare the effect of letrozole with combined metformin and clomiphene citrate (CC) for ovulation induction in CC-resistant women with polycystic ovary syndrome (PCOS).Design: A randomized controlled trial.Setting: University teaching hospital and a private practice setting.Patient(s): Two hundred fifty anovulatory women (582 cycles) with CC-resistant PCOS.Intervention(s): Patients received 2.5 mg of letrozole daily (123 patients, 285 cycles) or combined metformin–CC (127 patients, 297 cycles) for three treatment cycles.Main Outcome Measure(s): Ovulation rate, number of follicles, serum E2, serum P, endometrial thickness, pregnancy, and miscarriage rates.Result(s): Ovulation occurred in 185/285 cycles (64.9%) in the letrozole group versus 207/297 cycles (69.6%) in the combined metformin–CC group, without statistically significant difference. The total number of follicles was significantly more in the combined metformin–CC group (4.4 ± 0.4 vs. 6.8 ± 0.3). A nonsignificant increase in endometrial thickness on the day of hCG administration was observed in the letrozole group (9.5 ± 0.2 mm vs. 9.1 ± 0.1 mm). No statistically significant difference regarding the pregnancy rate (PR) was observed between both groups (14.7% vs. 14.4%).Conclusion(s): Letrozole and combined metformin–CC are equally effective for inducing ovulation and achieving pregnancy in patients with CC-resistant PCOS.

Multivariate analysis of factors affecting probability of pregnancy and live birth with in vitro fertilization: an analysis of the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System

2009-09-09

Objective: To evaluate factors predictive of clinical pregnancy and of pregnancy loss from assisted reproductive technology (ART) using data from the Society for Assisted Reproductive Technology database for 2004–2006.Design: Retrospective cohort.Setting: Clinic-based data.Patient(s): The study population included 225,889 fresh embryo transfer cycles using autologous oocytes and partner semen.Intervention(s): None.Main Outcome Measure(s): Clinical intrauterine gestation (presence of gestational sac) and live birth (≥22 weeks gestation and ≥300 g birth weight).Result(s): Increasing maternal age was significantly associated with a reduced odds of conception and increased fetal loss until 19 weeks gestation, but not with later pregnancy loss. Intracytoplasmic sperm injection (ICSI), assisted hatching, and increasing number of embryos transferred had significant positive effects on the odds of conception and pregnancy continuation through the first trimester, but did not affect the risk of later loss. Blacks, Asians, and Hispanics had significantly lower odds of clinical pregnancy compared with whites. Also compared with whites, Hispanics and Asians had a significantly greater risk of pregnancy loss in the second and third trimesters, and blacks had a significantly greater risk of pregnancy loss in all trimesters.Conclusion(s): Certain demographic and ART treatment parameters influenced chance of conception and early pregnancy loss, whereas black race and Hispanic ethnicity were also significantly associated with late pregnancy loss in ART-conceived pregnancies.

Polycystic ovary syndrome and cardiovascular risk in young patients treated with drospirenone-ethinylestradiol or contraceptive vaginal ring. A prospective, randomized, pilot study

2009-07-09

Objective: To compare the effects of a pill containing drospirenone with those of a combined contraceptive vaginal ring on the lipid and carbohydrate metabolism and on the surrogate markers of arterial function.Setting: Bologna University School of Medicine.Patient(s): Thirty-seven women with polycystic ovary syndrome (PCOS) were randomly submitted to drospirenone + ethinylestradiol (group I; n = 19) or combined contraceptive vaginal ring (group II; n = 18) therapy. The duration of the study was 6 months.Intervention(s): The effect of treatments was assessed after 6 months of therapy.Main Outcome Measure(s): Utero-ovarian ultrasound analysis and color Doppler evaluation of uterine and stromal ovarian arteries. In addition, analysis of brachial artery flow-mediated vasodilatation and 24-hour ambulatory blood pressure monitoring were performed. Fasting blood samples were drawn for testing biochemical and hormonal parameters and nitrites/nitrates.Result(s): Both treatments improved hirsutism, hyperandrogenemia, and ultrasound and color Doppler ovarian parameters. Both drospirenone + ethinylestradiol or contraceptive vaginal ring induced a slight but significant increase of diurnal and 24-hour blood pressure. Although both therapies worsened the lipid profile, the oral pill administration was associated with a more evident increase of circulating triglycerides. The 6-month treatment with the vaginal ring significantly improved the area under the curve for glucose, insulin, and C-peptide, whereas the drospirenone + ethinylestradiol pill induced an increase in the insulinogenic index and homeostatic model assessment estimate for insulin resistance values.Conclusion(s): Vaginal hormonal contraception appears to be preferable to oral ethinylestradiol + drospirenone administration in hyperinsulinemic patients with PCOS.

Reproductive health of women electing bariatric surgery

2009-10-07

Objective: To describe the reproductive health history and characteristics of women having bariatric surgery and to determine whether this differs by age of onset of obesity.Design: Retrospective and cross-sectional analyses of self-reported survey data.Setting: Six sites of the Longitudinal Assessment of Bariatric Surgery-2 study.Patient(s): The study included 1,538 females having bariatric surgery.Intervention(s): None.Main Outcome Measure(s): Reported polycystic ovary syndrome (PCOS), pregnancy and fertility history, contraceptive use, and plans for pregnancies.Result(s): Mean age was 44.8 years (range, 18–78 years); mean body mass index was 47.2 kg/m2 (range, 33.8–87.3 kg/m2). PCOS had been diagnosed by a health care provider in 13.1% of subjects. Of women who had tried to conceive, 41.9% experienced infertility and 61.4% had a live birth after experiencing infertility. In the whole group, prior live birth was reported by 72.5%. Women who were obese by 18 years old were more likely to report PCOS and infertility and less likely to have ever been pregnant, compared with women who became obese later in life. Future pregnancy was important to 30.3% of women younger than 45 years, whereas 48.6% did not plan to become pregnant in the future. In the year before surgery, 51.8% used contraception.Conclusion(s): Self-reporting of obesity by age 18 appears to be related to reproductive morbidity. Women undergoing bariatric surgery have important reproductive health care needs, including reliable contraception and counseling about plans for postoperative pregnancy.

Embryo transfer practices in the United States: a survey of clinics registered with the Society for Assisted Reproductive Technology

2009-09-11

Objective: To gain a better understanding of factors influencing clinicians' embryo transfer practices.Design: Cross-sectional survey.Setting: Web-based survey conducted in December 2008 of individuals practicing IVF in centers registered with the Society for Assisted Reproductive Technology (SART).Patient(s): None.Intervention(s): None.Main Outcome Measure(s): Prevalence of clinicians reporting following embryo transfer guidelines recommended by the American Society for Reproductive Medicine (ASRM), prevalence among these clinicians to deviate from ASRM guidelines in commonly encountered clinical scenarios, and practice patterns related to single embryo transfer.Result(s): Six percent of respondents reported following their own, independent guidelines for the number of embryos to transfer after IVF. Of the 94% of respondents who reported routinely following ASRM embryo transfer guidelines, 52% would deviate from these guidelines for patient request, 51% for cycles involving the transfer of frozen embryos, and 70% for patients with previously failed IVF cycles. All respondents reported routinely discussing the risks of multiple gestations associated with standard embryo transfer practices, whereas only 34% reported routinely discussing single embryo transfer with all patients.Conclusion(s): Although the majority of clinicians responding to our survey reported following ASRM embryo transfer guidelines, at least half would deviate from these guidelines in a number of different situations.

Relationship between interleukin-6 levels and ambulatory blood pressure in women with polycystic ovary syndrome

2009-09-28

Objective: To determine 24-hour ambulatory blood pressures (ABP) in patients with polycystic ovary syndrome (PCOS) and its relationship with interleukin-6 (IL-6).Design: Prospective controlled study.Setting: University hospital.Patient(s): Fifty-four PCOS patients.Intervention(s): Ambulatory blood pressure monitoring was conducted. Anthropometric, hormonal, metabolic, and inflammatory parameters, including plasma IL-6, C-reactive protein (CRP), fibrinogen, and nitric oxide (NO), were measured in each subject.Main Outcome Measure(s): Ambulatory blood pressure and plasma IL-6, CRP, fibrinogen, and NO.Result(s): Serum IL-6 levels of PCOS women in the highest systolic blood pressure (SBP) quartile were significantly higher than those of women in the lowest SBP quartile. The high serum IL-6 levels (serum IL-6 level ≥5.1 pg/mL) were associated with a higher probability of raised SBP (≥126 mm Hg), with an odds ratio of 2.2 (95% confidence interval 0.8–7.9). The systolic and diastolic (DBP) blood pressures were significantly related to serum IL-6 levels. The IL-6 levels were positively and significantly correlated with serum CRP levels. Interleukin-6 and CRP were negatively and significantly correlated with serum NO levels.Conlusion(s): The results suggest that raised plasma IL-6 levels may be related to ambulatory SBP and DBP in PCOS.

Intercourse compliance, ovulation, and treatment success in the National Institute of Child Health and Human Development–Reproductive Medicine Network's Pregnancy in Polycystic Ovary Syndrome (PPCOS) Trial

2009-06-22

Objective: To investigate the relationship among intercourse compliance, ovulation, and the occurrence of pregnancy in the Reproductive Medicine Network's Pregnancy in Polycystic Ovary Syndrome (RMNPPCOS) Trial.Design: Post hoc data analysis of subjects in the Reproductive Medicine Network PPCOS Trial.Setting: Academic medical centers.Intervention(s): None.Patient(s): Six hundred twenty-six infertile women with polycystic ovary syndrome with a mean age of 28.1 ± 4 years and mean body mass index of 35.2 ± 8.7 kg/m2.Main Outcome Measure(s): Intercourse compliance, ovulation, and pregnancy.Result(s): Data on 2925 cycles were included in the analysis, of which 1340 were ovulatory cycles and 1585 were nonovulatory cycles. The rates of intercourse compliance in the PPCOS trial were similar across all treatment groups at all cycles except cycle 4. Among cycles with known ovulation status, 81.2% of patients were compliant with intercourse instructions. Patients were more intercourse compliant in those cycles during which ovulation occurred (83.2% vs. 79.4%). With regard to ovulatory cycles, there was no difference in the occurrence of pregnancy when comparing intercourse compliant versus intercourse noncompliant cycles.Conclusion(s): Intercourse compliance was not associated with the occurrence of pregnancy in ovulatory cycles in the PPCOS Trial. The occurrence of ovulation still remains a critical predictor for the occurrence of pregnancy.

Body mass index and intercourse compliance

2009-06-22

Objective: To investigate the relationship between body mass index and intercourse compliance in the Reproductive Medicine Network's Pregnancy in Polycystic Ovary Syndrome (RMN PPCOS) Trial.Design: Post hoc data analysis of subjects in the RMN PPCOS Trial.Setting: Academic medical centers.Intervention(s): None.Patient(s): Six hundred twenty-six infertile women with polycystic ovary syndrome (PCOS) with a mean age of 28.1 ± 4 years and mean body mass index (BMI) of 35.2 ± 8.7 kg/m2.Main Outcome Measure(s): Intercourse compliance and BMI.Result(s): Overall, body mass index was not associated with increased intercourse compliance. However, although patients with BMI ≥35 were less likely to ovulate than patients with BMI <35, they tend to be more compliant with intercourse frequency in ovulatory cycles than patients with BMI <35.Conclusion(s): BMI was not associated with intercourse compliance or noncompliance. An elevated BMI in infertile women with PCOS is not associated with poor intercourse compliance.

Visfatin and leptin levels in women with polycystic ovaries undergoing ovarian stimulation

2009-06-12

Objective: To detect the levels of visfatin and leptin in the serum as well as in the follicular fluid (FF) of polycystic ovary syndrome (PCOS) patients undergoing controlled ovarian stimulation and to compare them with the levels found in age- and weight-matched normally ovulating women under IVF treatment.Design: Prospective study.Setting: Assisted Reproduction Unit, Second Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital, Athens, Greece.Patient(s): Forty patients with diagnosed PCOS and 40 age- and weight-matched non-PCOS control women enrolled in the IVF program.Intervention(s): Blood and FF samples were collected from all subjects at oocyte retrieval.Main Outcome Measure(s): Visfatin and leptin levels were measured in serum and FF using ELISA.Result(s): Serum visfatin levels were significantly increased in women with PCOS, whereas FF visfatin levels, which were lower than serum levels, did not differ between groups. Serum leptin levels did not differ between groups and were lower than FF levels.Conclusion(s): Women with polycystic ovaries exhibit significantly increased serum visfatin and decreased FF leptin levels compared with control subjects of similar age and body mass index, indicating a probable role for visfatin in the general state of insulin resistance and a local contribution in the follicle for leptin in patients undergoing IVF treatment.

A prospective investigation into the reasons why insured United States patients drop out of in vitro fertilization treatment

Alice D. Domar, Kristin Smith, Lisa Conboy, Marie Iannone, Michael Alper — 2009-07-09

Objective: To determine the primary reason why insured patients drop out of IVF treatment in the United States and to identify methods to decrease such behavior.Design: Prospective patient survey.Setting: Private infertility clinic.Patient(s): Women under the age of 40 years, who had insurance coverage for at least three IVF cycles, who did not conceive and who did not return to the clinic for a third treatment cycle.Intervention(s): One hundred thirty-two eligible patients received a study packet of questionnaires in the mail.Main Outcome Measure(s): Subject responses to questionnaire.Result(s): Forty-seven subjects returned the questionnaire. The most common reason for terminating treatment was stress (39%). Subjects reported that the two main causes of stress were the toll that infertility took on the couples' relationship and being too anxious or depressed to continue. The top-rated suggestions for patient support were written information on how to deal with psychological stress and easy and immediate access to a psychologist or social worker.Conclusion(s): Patients undergoing IVF in the United States report similar reasons for terminating treatment as patients in Europe and Australia. However, this is the first study to gather patient suggestions for treating the problem.

Men's participation in psychologic counseling services offered during in vitro fertilization treatments

Irene Furman, Leslie Parra, Ariel Fuentes, Luigi Devoto — 2010-01-29

Objective: To assess frequency of male participation in psychologic support services during IVF treatments.Design: Retrospective descriptive study.Setting: University infertility clinic.Patient(s): A total of 284 low-income men receiving government-financed IVF.Intervention(s): Group counseling during treatment.Main Outcome Measure(s): Frequency of attendance to group counseling and perception of usefulness of the service.Result(s): One-half of the subjects enrolled in the counseling groups. There were no differences in clinical and demographic characteristics between attendants and nonattendants. Attendance was classified into three levels: occasional, intermediate, and consistent. Seventy-four percent of attendants fell into latter two categories. Significant differences were observed in frequency of attendance as a function of infertility etiology. Frequent attendants diagnosed with male-factor-only infertility were double the number of participants with female infertility. Over 90% of attendants reported the support groups as “highly useful” and recommended that future patients participate. Emotional disclosure, decreased social isolation, and increased marital closeness were main benefits of the group interventions.Conclusion(s): Men respond positively to group counseling. They persevere with psychologic assistance when the infertility etiology is man dependent. Group counseling stands out as highly effective for mitigating the emotional impact of infertility, particularly when it is offered as an integral part of the reproductive treatment.

Assessment of sperm factors possibly involved in early recurrent pregnancy loss

2009-06-22

Objective: To evaluate and compare standard sperm parameters, lipid peroxidation of sperm plasma membranes, antioxidant capacity of seminal plasma, and sperm chromatin integrity in ejaculates from men whose partners have a history of recurrent pregnancy loss and from a control group of men with recent fertility.Design: Descriptive study.Setting: Reproduction Program, University of Antioquia, Medellín, Colombia.Patient(s): Twenty-three couples with history of recurrent pregnancy loss and 11 men with recent fertility.Intervention(s): Semen samples from control men and men whose partner had a history of recurrent pregnancy loss were examined for differences in semen parameters, lipid peroxidation, antioxidant capacity, DNA fragmentation index, and sperm preparation.Main Outcome Measure(s): Migration-sedimentation method was used to collect motile spermatozoa from fresh ejaculates for examination for semen parameters.Result(s): Men from the control group had spermatozoa with higher percentage of normal sperm morphology, concentration, progressive motility, and antioxidant capacity compared with men from the recurrent pregnancy loss group, who had spermatozoa with higher teratozoospermia and higher lipid peroxidation. Motile sperm fractions from both groups had spermatozoa with better sperm parameters compared with freshly ejaculated sperm.Conclusion(s): This study strengthens the current literature associating sperm quality with recurrent pregnancy loss, and emphasizes the importance of evaluating male factor by tests such as lipid peroxidation and measuring antioxidant capacity of seminal plasma in addition to conventional sperm parameters.

Etiology of recurrent pregnancy loss in women over the age of 35 years

Kerri Marquard, Lynn M. Westphal, Amin A. Milki, Ruth B. Lathi — 2009-07-30

Objective: To determine the rate of embryonic chromosomal abnormalities, thrombophilias, and uterine anomalies in women over the age of 35 years with recurrent pregnancy loss (RPL).Design: Retrospective cohort study.Setting: Academic reproductive endocrinology and infertility clinic.Patient(s): Women ≥35 years old with ≥3 first trimester miscarriages.Intervention(s): None.Main Outcome Measure(s): Age, number of prior losses, cytogenetic testing of the products of conception (POC), uterine cavity evaluation, parental karyotype, TSH, and antiphospholipd antibody (APA) and thrombophilia testing. Aneuploidy in the POC in women with RPL was compared with sporadic miscarriages (≤2 losses) in women ≥35 years.Result(s): Among 43 RPL patients, there were 50 miscarriages in which cytogenetic analysis was performed. In the RPL group, the incidence of chromosomal abnormalities in the POC was 78% (39 out of 50) compared with a 70% incidence (98 out of 140) in the sporadic losses. Thrombophilia results in the RPL patients were normal in 38 patients, four patients had APA syndrome, and one had protein C deficiency. Forty out of 43 had normal uterine cavities. Both TSH and parental karyotypes were normal in all of the patients tested. When the evaluation of RPL included karyotype of the POC, only 18% remained without explanation. However, without fetal cytogenetics, 80% of miscarriages would have been unexplained.Conclusion(s): In older patients with RPL, fetal chromosomal abnormalities are responsible for the majority of miscarriages. Other causes were present in only 20% of cases.

Blockage of ghrelin-induced prolactin secretion in women by bromocriptine

2009-09-28

Objective: To investigate the effect of bromocriptine on ghrelin-induced PRL secretion in women.Design: Longitudinal study.Setting: University hospital.Patient(s): Ten healthy, normally cycling women.Intervention(s): The women were injected IV on day 3 of three cycles with a single dose of normal saline (cycle 1) or ghrelin (1 μg/kg) after pretreatment for 2 days either with placebo (cycle 2) or with bromocriptine (cycle 3) per os. Blood samples were taken before and frequently after drugs administration for 120 minutes.Main Outcome Measure(s): The PRL and GH responses to ghrelin were assessed.Result(s): Bromocriptine suppressed basal PRL levels significantly. The injection of ghrelin stimulated a significant increase in serum PRL levels in cycle 2 but not in cycle 3, in which PRL levels remained stable. The response of GH to gherlin was significantly attenuated in cycle 3 as compared with cycle 2.Conclusion(s): The present study demonstrates for the first time that bromocriptine blocked the stimulating effect of ghrelin on PRL release and attenuated the GH response to the same stimulus. The mechanism of these interactions needs to be clarified.

Anti-Müllerian hormone and inhibin B variability during normal menstrual cycles

2009-12-07

Objective: To describe anti-Müllerian hormone (AMH) variation across normal menstrual cycles.Design: Cohort study.Setting: Academic environment.Patient(s): Twenty regularly menstruating women.Intervention(s): Serum AMH and inhibin B assayed daily during one normal menstrual cycle.Main Outcome Measure(s): Intracycle variability of AMH and inhibin B.Result(s): Data were classified into quartiles of AMH area-under-the-curve (AUCs). Mean AMH AUC was 15.7 ng/mL for quartile 1 versus 43.5, 80.9 and 144.9 ng/mL for quartiles 2, 3, and 4. Mean AMH levels (ng/mL) were 0.67, 1.71, 3.02, and 5.33, respectively. There was no variation in quartile 1 AMH rate of change from stochastic modeling, but in quartiles 2 to 4, there were increased rates of change in days 2 to 7. Women in quartile 1 had the lowest mean inhibin B (24.2 pg/mL vs. 44.3, 43.2, and 42.2 pg/mL), and had shorter menstrual cycles (24.6 days) than women in quartiles 3 and 4 (28.2 and 28.4 days).Conclusion(s): There were two menstrual cycle patterns of AMH. The “aging ovary” pattern included low AMH levels with little variation, lower inhibin B, and shorter cycle lengths. The “younger ovary” pattern included higher AMH levels with significant variation days 2 to 7, suggesting that for women with AMH >1 ng/mL, the interpretation of AMH levels is contingent upon the day of the menstrual cycle on which the specimen is obtained.

Intraoperative contact ultrasonography during open myomectomy for uterine fibroids

2009-12-03

Objective: To evaluate the benefit of intraoperative ultrasound applied directly to the uterine serosa during surgery for uterine fibroids.Design: Prospective study.Setting: University hospital, tertiary care.Patient(s): Women admitted for open myomectomy due to uterine fibroids.Intervention(s): Intraoperative ultrasound (IUS) and intraoperative palpation were performed to detect the number of residual fibroids at the end of surgery, then the number of fibroids was recorded at anatomopathology examination.Main Outcome Measure(s): Residual fibroids detected at IUS and intraoperative palpation at the end of open myomectomy.Result(s): The comparison between the number of residual fibroids at IUS and at intraoperative palpation was statistically significant.Conclusion(s): Intraoperative ultrasound is more efficient than palpation in detecting residual leiomyomata at the end of open myomectomy.

Involvement of FKHR (FOXO1) transcription factor in human uterus leiomyoma growth

2009-09-22

Objective: To study the expression of FOXO1 and pSer256-FOXO1 parallel to Akt and pSer473-Akt in leiomyoma compared with adjacent myometrium from human uteri.Design: Prospective study.Setting: University departments.Patient(s): Thirty-eight cyclic and 20 menopausal women who underwent hysterectomy for benign indications.Intervention(s): None.Main Outcome Measure(s): Western blot analyses were used for evaluation in leiomyoma and adjacent myometrium of Akt and pSer473-Akt, 14-3-3 γ proteins and expression and subcellular distribution of FOXO1 and pSer256-FOXO1 during the menstrual cycle and at menopause.Result(s): The present study demonstrates the expression of FOXO1 and pSer256-FOXO1 at the tissue level in the human uterus leiomyoma and adjacent myometrium. The level of phosphorylated FOXO1 in leiomyoma was higher than in matched myometrium. The pSer256-FOXO1 in leiomyoma during menstrual phases was located mostly in the nuclear fraction comparison to that of the myometrium. The reason for this difference is presumably the simultaneously detected lower level of 14-3-3 protein.Conclusion(s): Abundant level of the phosphorylated FOXO1, its impaired nucleocytoplasmic shuttling, and the lowered expression of 14-3-3 protein in leiomyoma induces a shift in the cellular machinery toward a prosurvival execution program and thus presents a potential therapeutic target for treatment of leiomyoma.

GnRH analogue treatment before hysteroscopic resection of submucous myomas: a prospective, randomized, multicenter study

2009-06-22

Objective: To evaluate the efficacy of GnRH analogue treatment before hysteroscopic resection of submucous myomas in patients with abnormal uterine bleeding.Design: Multicenter, prospective, randomized, clinical study.Setting: Tertiary-care university hospitals.Patient(s): Thirty-nine consecutive patients with submucous myomas graded as G0 or G1 according to the European Society for Gynecological Endoscopy classification (myoma size 10–35 mm).Intervention(s): Patients were randomized to either direct surgery or 2 months of GnRH analogues before undergoing hysteroscopic resection of the submucous myoma.Main Outcome Measure(s): Operating times, fluid absorption, difficulty of the operation, surgeon satisfaction with the procedure, intra- and postoperative complications, postoperative pain, and patient satisfaction were recorded.Result(s): Patients treated with GnRH analogue had significantly shorter operative times (15.9 ± 3.1 minutes vs. 21.3 ± 4.0 minutes) and significantly reduced fluid absorption (378 ± 137 mL vs. 566 ± 199 mL) compared with no preoperative medical treatment. Operative difficulty and overall surgeon satisfaction were significantly better in the GnRH analogue group. Patient satisfaction was similar in the two groups.Conclusion(s): GnRH analogue treatment before hysteroscopic resection of G0-G1 10–35 mm submucous myomas was effective in reducing operative times, fluid absorption, and difficulty of the procedure.

Racial diversity in uterine leiomyoma clinical studies

F. Andrei Taran, Haywood L. Brown, Elizabeth A. Stewart — 2009-12-07

Objective: To examine racial diversity in clinical studies on uterine leiomyomas included in a review of evidence-based practice because of the disproportionate burden of fibroids in Black women.Design: Review of 106 studies cited in the Agency for Healthcare Research and Quality (AHRQ) report on uterine leiomyomas.Setting: Academic medical centers.Patient(s): None.Intervention(s): Estimation of the racial diversity of enrollment in studies on leiomyomas that did not report racial composition by two hypothetical models.Main Outcome Measure(s): Representation of Black women in studies from the AHRQ report.Result(s): Of the 106 analyzed studies, 81 studies did not report patients' race or ethnicity. Twenty-two of the 25 studies with reported race or ethnicity included Black participants. Analysis of studies reporting race and ethnicity, including studies specifically of African-American women, suggests that Black women comprise approximately half of all study participants. However, when estimating the proportion of Black women based on population demographics in each country, the representation of Black women in clinical leiomyoma studies appears to be closer to 15%.Conclusion(s): Most studies on uterine leiomyomas cited in the AHRQ evidence-based report did not report participation by race or ethnicity.

Effect of testis nondescent or orchidopexy on antisperm antibodies and testis histology in rats

2009-09-07

Objective: To examine effects of nondescent of normal testis and of various orchidopexy techniques on antisperm antibody (ASA) production and histologic testicular lesions.Design: Experimental cohort study.Setting: Laboratories of surgical research and biology of reproduction, academic medical centers.Patient(s): Lewis rats, immature and adult.Intervention(s): Eighteen-day-old rats (6 groups): intra-abdominal stay of testis after closure of inguinal canal, classic dartos pouch orchidopexy, orchidopexy by testis fixation through tunica albuginea, orchidopexy by transparenchymal testicular fixation, sham operation, and bilateral vasectomy. Adult rats (1 group): transparenchymal testicular fixation.Main Outcome Measure(s): The ASA—antiacrosome and antitail—were measured by indirect immunofluorescence in sera collected preoperatively, on 50th and 120th day in immature rats, and 90 days after surgery in adult rats. Testicular histology was also examined at the end of sera collection.Result(s): Neither intra-abdominal testicular localization nor orchidopexies induced significant ASA. Testicular nondescent and fixation (transparenchymal or transtunical) caused hypospermatogenesis; dartos pouch was harmless. Bilateral vasectomy produced significantly increased ASA, but no significant testicular lesions. Contralateral testes were unaffected.Conclusion(s): Intra-abdominal testicular stay and orchidopexy do not elicit autoimmune response to sperm; histologic testicular lesions might not be associated with ASA. In operated cryptorchids, ASA are probably due to other reason than testicular heat or orchidopexy trauma.

Calcium-binding protein S100P is highly expressed during the implantation window in human endometrium

Xiao-Mei Tong, Xiao-Na Lin, Tao Song, Liu Liu, Song-ying Zhang — 2009-09-30

Objective: To investigate S100P expression and localization in human endometrium throughout the menstrual cycle.Design: Experimental study.Setting: University hospital.Patient(s): Eighty-four women.Intervention(s): Complementary DNA (cDNA) microarray analysis was performed on human endometrium from days LH+4, LH+7, and hCG+7. Reverse transcriptase–polymerase chain reaction (RT-PCR) and Western blot analysis were used to detect the expression of S100P and of additional S100 family members, S100A4, S100A13, and S100A6. Immunofluorescence was used to detect the localization of S100P protein in LH+7 and LH+4 endometrium.Main Outcome Measure(s): Differential gene expression, levels of S100P messenger RNA (mRNA), and protein expression and immunofluorescent localization of S100P.Result(s): A statistical method, based on hierarchical clustering, identified genes whose expression varied at LH+7 compared with LH+4. We found that S100P was the fourth most up-regulated gene at LH+7. The S100P mRNA and protein levels were quite low during the proliferative phase and LH+4, but were elevated significantly at LH+7. The S100P expression at hCG+7 was lower than that at LH+7. However, the expression of S100A4, S100A13, and S100A6 did not vary throughout the menstrual cycle.Conclusion(s): S100P was specifically up-regulated during the implantation window. The underlying biological effects of S100P need further exploration.

Amenorrhea and “man hands”

Henry Bohler, Carreen Attaway-Drake — 2010-03-19

A 36-year-old multiparous woman presented with amenorrhea and hyperhidrosis of 6 months' duration. Physical examination revealed large, stubby fingers and toes with soft tissue thickening. Serum growth hormone and insulin-like growth factor-1 (IGF-1) levels were elevated and a pituitary macroadenoma was found on computerized tomography (CT).

Efficacy of a novel educational curriculum using a simulation laboratory on resident performance of hysteroscopic sterilization

Scott G. Chudnoff, Connie S. Liu, Mark D. Levie, Peter Bernstein, Erika H. Banks — 2009-09-28

Objective: To assess whether a novel educational curriculum using a simulation teaching laboratory improves resident knowledge, comfort with, and surgical performance of hysteroscopic sterilization.Design: An educational prospective, pretest/posttest study.Setting: The Montefiore Institute of Minimally Invasive Surgery Laboratory.Patient(s)/Subject(s): Thirty-four OB/GYN residents in an academic medical center.Intervention(s): Hysteroscopic sterilization simulation laboratory and a brief didactic lecture.Main Outcome Measure(s): Differences in scores on validated skill assessment tools: Task specific checklist, Global Rating Scale (GRS), pass fail assessment, and a multiple-choice examination to evaluate knowledge and attitude.Result(s): In the entire cohort improvements were observed on all evaluation tools after the simulation laboratory, with 31% points (SD ± 11.5, 95% confidence interval [CI] 27.3–35.3) higher score on the written evaluation; 63% points (SD ± 15.7, 95% CI 57.8–68.8) higher score on the task specific checklist; and 54% points (SD ± 13.6, 95% CI 48.8–58.3) higher score on the GRS. Higher PGY status was correlated with better pretest performance, but was not statistically significant in posttest scores. Residents reported an improvement in comfort performing the procedure after the laboratory.Conclusion(s): Simulation laboratory teaching significantly improved resident knowledge, comfort level, and technical skill performance of hysteroscopic sterilization.

Sterilization of liquid nitrogen with ultraviolet irradiation for safe vitrification of human oocytes or embryos

2009-07-09

Objective: To evaluate the efficacy of ultraviolet (UV) irradiation for rapid microbial decontamination of liquid nitrogen (LN2).Design: Basic research.Setting: Private assisted reproduction center.Animal(s): Microorganisms (bacteria and fungi).Intervention(s): Two stainless steel open dewars containing LN2 were contaminated in a two-step experiment with high titers of cultures of bacteria (Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Escherichia coli) and fungi (Aspergillus niger). One of the two dewars was subsequently exposed to UV irradiation at 253.7 nm to obtain a rapid microbial decontamination before the complete evaporation of LN2.Main Outcome Measure(s): Detection of the micro-organisms in LN2 after UV sterilization through the assessment of bacterial and fungal growth in minimal and selective Petri dishes.Result(s): None of the contaminating micro-organisms were detected in LN2 after UV sterilization.Conclusion(s): Decontamination of LN2 with UV irradiation is feasible and straightforward. The fact that LN2 can be quickly and safely sterilized should encourage the wider application of human oocyte and embryo vitrification with “open carriers.”

Klinefelter's syndrome with unilateral absence of vas deferens

Numan Baydilli, Ahmet Gökçe, Sevda Yesim Karabulut, Oguz Ekmekcioglu — 2010-03-23

Objective: To report a case of Klinefelter's syndrome with unilateral absence of vas deferens.Design: Case report.Setting: Tertiary-care infertility clinic.Patient(s): A 28-year-old man with the complaint of infertility.Intervention(s): None.Main Outcome Measure(s): Physical examination, genetic and hormonal evaluation.Result(s): Both testicles were approximately 2 mm, and unilateral vas deferens was not palpable. Hormonal evaluation revealed hypergonadotropism, and genetic studies revealed a 47,XXY karyotype and delta F508 mutation of the cystic fibrosis gene.Conclusion(s): To our knowledge there are no previous reports of both conditions (Klinefelter's syndrome and unilateral absence of vas deferens) existing simultaneously. A detailed physical examination seems mandatory for patients seeking treatment for infertility, to determine any possible deleterious health-related condition(s) for both themselves and offspring.

Septic shock due to Klebsiella pneumoniae after medical abortion with misoprostol-only regimen

Apostolos Kaponis, Stefania Papatheodorou, George Makrydimas — 2010-03-19

Objective: To report a case of a healthy woman who was admitted to the hospital with septic shock caused by a common uropathogen after self-administration of misoprostol for pregnancy termination.Design: Case report.Setting: Tertiary hospital.Patient(s): A 38-year-old woman, gravida 5, para 3, who developed septic shock after medical termination of pregnancy.Intervention(s): Suction curettage, antibiotic treatment, plasma and platelet transfusions.Main Outcome Measure(s): Klebsiella pneumoniae was isolated from blood samples.Result: Ten days after her admission she was discharged home in good condition on oral antibiotics.Conclusion(s): Severe infections leading to septic shock from common pathogen bacteria can occur after medical termination of pregnancy, independently of the regimen used.

Endometriomas in adolescents

Kelly Nicole Wright, Marc R. Laufer — 2010-03-23

Objective: To report a rare presentation of bilateral endometriomas in an adolescent and describe characteristics of endometriomas.Design: Case report.Setting: Major academic medical center.Patient(s): An 18-year-old G0 presented with an incidentally found 35-cm pelvic mass that was found to be bilateral endometriomas.Intervention(s): Exploratory laparotomy with resection of endometrioma cyst walls and lysis of adhesions.Main Outcome Measure(s): The incidence, pathogenesis, fertility implications, and treatment options for endometriomas in adolescents.Result(s): Endometriomas are rare in adolescents. There are no case reports in the literature to date.Conclusion(s): Endometriosis should be considered in adolescents presenting with bilateral complex ovarian masses regardless of their size.

Preimplantation genetic diagnosis for a carrier of a Y;autosome translocation resulting in a healthy male offspring

2010-03-24

Objective: To demonstrate the feasibility of establishing a successful pregnancy for a carrier of a balanced Y;autosome translocation.Design: Four locus-specific fluorescence in situ hybridization (FISH) probes, informative for the translocation, were identified and tested on peripheral lymphocyte metaphase chromosomes and interphase preparations from the translocation carrier and his partner.Setting: National health service genetics center, cytogenetics laboratory, and assisted conception unit.Patient(s): An infertile man, presenting with a balanced Y;13 translocation, and his reproductive partner.Intervention(s): After ovarian stimulation, 15 eggs were collected, nine were injected, and three were suitable for blastomere biopsy on day 3; a single blastomere was taken from each embryo and tested with four locus-specific FISH probes.Main Outcome Measure(s): Birth of a healthy child.Result(s): One embryo showed a triploid signal pattern and one had fragmented nuclei; neither was suitable for transfer. One embryo showed a balanced male signal pattern and was transfered. A singleton pregnancy was established, resulting in the birth of a healthy male child.Conclusion(s): This first report of successful preimplantation genetic diagnosis treatment for infertile males with y:autosome translocations demonstrates that this treatment option can result in successful pregnancies and healthy offspring.

Hysteroscopic management of heterotopic cesarean scar pregnancy

Chin-Jung Wang, Fengpo Tsai, Chaowen Chen, Angel Chao — 2010-03-29

Objective: To report a cesarean scar pregnancy (CSP) with a coexistent viable intrauterine pregnancy.Design: Case report.Setting: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou, Taiwan.Patient(s): A 31-year-old woman, with previous cesarean delivery, presented with vaginal bleeding, was transferred to our hospital at 7 weeks' gestation for heterotopic pregnancy after an IVF–embryo transfer. A diagnosis of intrauterine pregnancy combined with CSP was made by ultrasonography.Intervention(s): Hysteroscopic-directed evacuation of CSP.Main Outcome Measure(s): Good hemostasis at cesarean site and ongoing intrauterine pregnancy.Result(s): A healthy baby was delivered by cesarean delivery at term.Conclusion(s): With the increasing number of IVF–embryo transfers, the amount of heterotopic pregnancies is also increasing. Hysteroscopic management of CSP is a minimally invasive procedure that leads to successful obstetric outcomes in the corresponding intrauterine pregnancies.

Increased levels of oxidants and reduced antioxidants in semen of infertile men with varicocele

Mohamed Ahmed Abd-Elmoaty, Ramadan Saleh, Rakesh Sharma, Ashok Agarwal — 2010-02-01

Significantly higher levels of oxidants (malonaldehyde and nitric oxide) and reduced levels of antioxidants (superoxide dismutase, glutathione peroxidase, catalase, and ascorbic acid) are seen in semen of infertile men with varicocele. Seminal oxidative stress (OS) seen in men with varicocele is associated with sperm motility and grade of varicocele.

Detection of enlarged yolk sac on early ultrasound is associated with adverse pregnancy outcomes

Danielle M. Berdahl, Jill Blaine, Bradley Van Voorhis, Anuja Dokras — 2010-02-15

Pregnancies with mean yolk sac diameter ≥5 mm on early ultrasound require monitoring and counseling about a threefold increased risk for first-trimester loss independent of maternal risk factors such as age, body mass index, polycystic ovary syndrome, smoking, and diabetes. In addition, our study shows for the first time that enlarged yolk sac diameter may be associated with an increased risk of preterm delivery.

Endometrial stromal progesterone receptor-A/progesterone receptor-B ratio: no difference between women with and without endometriosis

2010-01-25

The aim of the present study was to investigate whether alterations of the P receptor–A/P receptor–B ratio could be considered an etiopathogenetic factor for endometriosis. We failed to observe statistically significant differences in both P receptor–A/P receptor–B messenger RNA and protein ratio between endometrial stromal cells derived from women with and without endometriosis.

Reactive oxygen species levels are independent of sperm concentration, motility, and abstinence in a normal, healthy, proven fertile man: a longitudinal study

Nisarg R. Desai, Reda Mahfouz, Rakesh Sharma, Sajal Gupta, Ashok Agarwal — 2010-02-01

In a longitudinal study over a period of 21 months, we demonstrated that seminal reactive oxygen species (ROS) levels are independent of sperm concentration, motility, and abstinence duration within a healthy sperm donor, although some variations were observed in ROS levels. We suggest that fluctuation in seminal ROS values may be related to physiologic or transient changes in spermatogenesis.

Circulating maternal testosterone concentrations at 18 weeks of gestation predict circulating levels of antimüllerian hormone in adolescence: a prospective cohort study

2010-02-15

This prospective study was established to determine the impact of maternal circulating androgen levels during normal pregnancy on ovarian function, as determined by early follicular phase antimüllerian hormone (AMH) levels, inhibin B levels, and antral follicle count (AFC) in 244 female offspring in adolescence. Maternal circulating total testosterone levels at 18 weeks' gestation were statistically significantly correlated with early follicular-phase circulating AMH levels in female adolescent offspring, but no other statistically significant correlations were determined among the maternal androgens at 18 or 34 weeks of gestation and the markers of adolescent ovarian function.

Ultrastructural deformity of ovarian follicles induced by different cryopreservation protocols

Gil Ah Kim, Hwa Young Kim, Jee Woong Kim, Gene Lee, Eunsong Lee, Jeong Mook Lim — 2010-01-27

Ultrastructural deformities were monitored after cryopreservation of F1 (B6CBAF1) mouse ovaries by either slow freezing or vitrification. Vacuole formation in the ooplasm, zona pellucida, and the cytoplasm of follicular cells, and mitochondrial deformity were detected. These types of cryodamage demonstrated protocol specificity.

The first community-based report on the effect of genital Schistosoma haematobium infection on female fertility

2010-02-10

A cross-sectional study in an Schistosoma haematobium endemic area of rural Zimbabwe examined 483 resident women between the ages of 20 and 49 years who were interviewed about fertility. S. haematobium ova in genital tissue was found to be significantly associated with infertility.

Failure of the GnRH antagonist ganirelix to block the positive feedback effect of exogenous estrogen in normal women

2010-02-10

This study investigated whether the GnRH antagonist ganirelix is able to block the positive-feedback effect of E2 in normal women. Ganirelix was unable to block the positive-feedback effect, suggesting that the clinical efficacy of GnRH antagonists in IVF cycles is determined by the hyperstimulation process.

Markers of ovarian reserve in young girls with Turner's syndrome

Radhika Purushothaman, Oksana Lazareva, Kutluk Oktay, Svetlana Ten — 2010-01-25

We describe a preliminary report identifying markers of ovarian reserve to identify candidates for ovarian cryopreservation. Among 14 patients with Turner's syndrome, those with a poor probability of fertility had a significantly higher FSH, lower inhibin A, and lower AMH compared with those with a fair probability of fertility.

Polymorphisms in MMP-2 and MMP-9 promoter regions are associated with endometriosis

2010-01-25

In this case-control study, we investigated the potential associations of MMP-2 and MMP-9 gene promoter region polymorphisms as well as MMP-2 promoter haplotypes with susceptibility to endometriosis in women of caucasian origin. The results demonstrated that polymorphisms in MMP-2 (−735 C/T) and MMP-9 (−1562 C/T) were associated with elevated risk of endometriosis and that certain MMP-2 promoter haplotypes were more common in control group.

Variability in anti-Müllerian hormone levels: a comment on Sowers et al., Anti-Müllerian hormone and inhibin B variability during normal menstrual cycles

Stephen A. Roberts — 2010-07-14

To the Editor: The article by Sowers et al. presents valuable and carefully collected data on the variability of serum anti-Müllerian hormone (AMH) over the menstrual cycle, with 20 women each providing daily blood samples for one complete cycle. It is unfortunate that sampling was not prolonged to obtain data for all or part of a second cycle, which would have allowed them to estimate repeatability and obtain rigorous statistical tests of cycle effects; this should be considered for future similar studies.

Reply of the authors: Variability in anti-Müllerian hormone levels: a comment on Sowers et al., Anti-Müllerian hormone and inhibin B variability during normal menstrual cycles

2010-07-14

We thank Dr. Roberts for his interest in our paper Anti-Müllerian hormone and inhibin B variability during normal menstrual cycles that describes variability in anti-Müllerian hormone (AMH) measured daily across the menstrual cycle in 20 women, aged 30–39 years, who reported having regular menstrual cycles in the previous year . In his Letter to the Editor , Dr. Roberts urges that data from more than one cycle be collected to determine between-cycle differences. We acknowledge that multiple cycles in the same women are an optimal way of describing between-cycle patterns, although the implementation of these studies requiring daily sampling of blood and urine across months is rather challenging. It is true that a single cycle of daily AMH measures may not reflect a represent pattern of cycle length and variability in AMH measures in a given woman; however, the AMH measures may represent follicle development that takes place over several months , and that variability in measures of AMH may reflect the heterogeneity of follicular phase follicle-stimulating hormone, which in perimenopausal women, represents a mixture of ovulatory and anovulatory cycles. In designing this study, we believed there were three strengths that helped assure that the data from a single cycle were informative and would minimize the likelihood of confounding from anovulatory cycles. First, the age of the healthy participants was 30–39 years. Second and most importantly, each woman reported a history of established menstrual cycle regularity that was sustained in the year preceding study entry. Third, AMH was measured daily across the menstrual cycle, including the follicular phase. We suggest these design strengths be considered favorably in the interpretation of these data.

It is time to respect the American Society for Reproductive Medicine definition of recurrent pregnancy loss

Helena von Eye Corleta — 2010-07-15

To the Editor: We read with great interest the article by Jaslow et al. . They proposed to determine whether the frequency of abnormal results for evidence-based diagnostic tests differed among women with recurrent pregnancy loss (RPL) on the basis of the number of prior losses (N = 2, 3, or >4).

Has B-Lynch suture hidden long-term effects?

Loïc Sentilhes, Philippe Descamps, Loïc Marpeau — 2010-07-15

To the Editor: We read with great interest the case reported by Goojha et al. , and we could not agree more with the authors regarding the necessity to adequately assess subsequent fertility after B-Lynch suture. Whereas B-Lynch suture was adopted promptly throughout the world, we have been attempting to alert physicians to the possible hidden midterm or long-term effects of uterine compression sutures . The aim of a uterine-sparing procedure is not only to control postpartum hemorrhage with the lowest morbidity but also to preserve a theoretical functional uterus that will not compromise the patients' subsequent fertility and obstetric outcome. It is essential to note that currently no studies have assessed fertility adequately after uterine compression sutures , whereas there are validated data showing that uterine artery ligation for postpartum hemorrhage does not appear to compromise these two decisive parameters . In fact, there are only isolated cases that have reported successful (or unsuccessful) pregnancies after B-Lynch suture , and no studies yet have taken into consideration the evaluation of desire and attempts to conceive. Contrary to Goojha et al. , we do not believe that a registry will be sufficient to resolve this issue, because no information will be available regarding women with presumed preserved fertility and desire for pregnancy who do not become pregnant, thus resulting in an impossibility to adequately assess subsequent fertility after B-Lynch suture. Unfortunately, only systematic follow-up of a relatively large cohort of women who have undergone a B-Lynch suture, as previously performed for long-term assessment of other uterine-sparing procedures , will determine whether B-Lynch suture is associated with hidden midterm or long-term effects. These data are essential to establish the place of B-Lynch suture in the postpartum hemorrhage surgical management algorithm .

Transforming growth factor β1 gene -509 C/T polymorphism and endometriosis

Andrea Romano, Kim J.A.F. van Kaam, Gerard A.J. Dunselman — 2010-07-20

To the Editor: We read with interest the article by Kim and co-workers describing the analysis of the transforming growth factor β1 (TGF-β1)-509 C/T gene polymorphism among Korean patients with advanced stage endometriosis and controls. The authors assessed the prevalence of the C/C, C/T and T/T genotypes among 485 cases and 352 controls and found no association with endometriosis: CC/CT/TT rates were 29.3%/48.2%/22.5% and 27.3%/50.3%/22.4% for the endometriosis and control groups, respectively. Their results contradict a previous study that found a strong association between endometriosis and the presence of the -509T allele in a Chinese population.

Reply of the Authors: Transforming growth factor β1 gene -509 C/T polymorphism and endometriosis

Young Min Choi — 2010-07-20

My colleagues and I have read the comment by Romano et al. directed to our article entitled “Analysis of the transforming growth factor -β1 gene -509 C/T polymorphism in patients with advanced-stage endometriosis.”

Relevance of the site of assisted hatching in thawed human blastocysts

Thomas Ebner, Omar Shebl, Richard Bernhard Mayer, Gernot Tews — 2010-07-23

To the Editor: We read with interest the elegant paper of Miyata et al. in which they reported the existence of polarity in the hatching process of warmed human blastocysts. In detail, artificial zona pellucida (ZP) opening close to the inner cell mass (ICM) resulted in improved rates of complete hatching whereas assisted hatching at the abembryonic site caused trapping of the embryo within the ZP .

Reply of the Authors: Relevance of the site of assisted hatching in thawed human blastocysts

2010-07-23

We would like to express our thanks to Ebner et al. for their interest in our paper on the existence of polarity in the hatching process of thawed human blastocysts . Our data from a prospective randomized study of assisted hatching (AH) of thawed human blastocysts (N = 32) demonstrated that the rate of complete hatching was significantly higher for AH performed near the inner cell mass (ICM) than for AH at the side opposite to the ICM . In thawed blastocysts without AH (N = 13), initiation of hatching occurred almost equally at sites near and opposite the ICM. Extrusion of the ICM and complete hatching, however, were only observed near the ICM . Our study had the limitations of a small sample size, the use of frozen embryos, and the in vitro nature of the study. Moreover, we did not know whether pregnancy or implantation would be related to the hatching site because we did not attempt any transfer of the studied blastocysts. The study by Ebner et al. seemed to compensate for these limitations. Using fresh blastocysts without AH (N = 108), they reported that a significantly higher clinical pregnancy rate was observed if blastocysts that hatched close to the ICM were transferred as compared with their counterparts that herniated from the mural trophectoderm . This finding strengthens the evidence supporting the existence of polarity in the hatching process of human blastocysts.

Orthodox Judaism does not necessarily prohibit all multifetal reductions

Richard V. Grazi, Joel B. Wolowelsky — 2010-08-02

To the Editor: In their discussion of infertility counseling for Orthodox Jews, Haimov-Kochman et al. note that, in regard to multifetal pregnancy reduction, one soul cannot be put aside for the sake of another and that discussion of the number of embryos to be transferred to the womb should include the religious obstacle to reduce the number of embryos later during early pregnancy.

Improving of pregnancy rate by modifying embryo transfer technique

Lionel Dessolle — 2010-08-06

To the Editor: I read with great interest the paper by Madani et al. . The authors report a randomized controlled study of 110 women in which pushing 0.2 mL of air into the uterus after embryo transfer (ET) was associated with a significant improvement of the clinical pregnancy rate from 9/55 (16.4%) in the control group to 22/55 (40%) in the study group.

Reply of the Authors: Improving of pregnancy rate by modifying embryo transfer technique

Tahereh Madani — 2010-08-06

We thank Dr. Lionel Dessolle for his constructive comments. We express our regret for not stating the registration number in the manuscript. The identifier is NCT00905788, which can be found on ClinicalTrials.gov.

Ongoing pregnancy after human menopausal gonadotropin stimulation and timed intercourse in a 40-year-old woman with undetectable antimüllerian hormone levels

Tim Cordes, Askan Schultze-Mosgau, Klaus Diedrich, Georg Griesinger — 2010-08-06

To the Editor: We read with interest the articles published in Fertility and Sterility by Fraisse et al. and Tocci et al. who reported on a total of three pregnancies that occurred in the presence of undetectable levels of serum antimüllerian hormone (AMH). We would like to bring a similar case to the attention of our colleagues.

Reply of the Authors: Ongoing pregnancy after human menopausal gonadotropin stimulation and timed intercourse in a 40-year-old woman with undetectable antimüllerian hormone levels

2010-08-06

We warmly thank Cordes et al. for adding a new case to those of our original report, which first presented the possibility of ongoing pregnancies in women who have undetectable levels of antimüllerian hormone (AMH) . We, too, have identified 10 additional, similar cases, four of whom were fertile women, since our first report was published.

Reply of the Authors: Ongoing pregnancy after human menopausal gonadotropin stimulation and timed intercourse in a 40-year-old woman with undetectable antimüllerian hormone levels

Angelo Tocci — 2010-08-06

We thank Dr. Cordes and colleagues for their interest in our paper . They present a case of a 40-year-old hypergonadotropic woman with secondary infertility who achieved pregnancy by slight controlled ovarian hyperstimulation (COH) and timed intercourse in the presence of undetectable levels of antimüllerian hormone (AMH). In the opinion of Cordes et al., their case corroborates the hypotheses that undetectable AMH levels cannot predict fecundity and should not imply the use of in vitro fertilization (IVF) as a first option.

American Society for Reproductive Medicine 2010 Calendar

2010-09-01

For more information, contact: American Society for Reproductive Medicine

Editorial Board

2010-09-01

Alan H. DeCherney, M.D. Bethesda, Maryland

2010-09-01