Fertility and Sterility - Articles in Press

Perinatal outcome of singleton siblings born after assisted reproductive technology and spontaneous conception: Danish national sibling-cohort study - Corrected Proof

2010-09-02

Objective: To compare the perinatal outcome of singleton siblings conceived differently.Design: National population-based registry study.Setting: Denmark, from 1994 to 2008.Patient(s): Pairs of siblings (13,692 pairs; n = 27,384 children) conceived after IVF, intracytoplasmatic sperm injection (ICSI), frozen embryo replacement (FER), or spontaneous conception subcategorized into five groups according to succession: [1] IVF-ICSI vs. spontaneous conception (n = 7,758), [2] IVF-ICSI vs. FER (n = 716), [3] FER vs. FER (n = 34), [4] IVF-ICSI vs. IVF-ICSI (n = 2,876), and [5] spontaneous conception vs. spontaneous conception (n = 16,000).Intervention(s): Observations were obtained from national registries.Main Outcome Measure(s): Birth weight, gestational age, low birth weight (<2,500 g), preterm birth (<37 weeks’ gestation) and perinatal deaths.Result(s): Mean birth weight was 65 g (95% confidence interval [CI], 41–89] lower in all assisted reproductive technology children compared with their spontaneously conceived siblings. FER children were 167 g (95% CI, 90–244] heavier than siblings born after replacement of fresh embryos. The difference in birth weight between firstborn and second born sibling depended on order of conception method. Higher risk of low birth weight with (odds ratio [OR], 1.4; 95%CI, 1.1–1.7] and preterm birth (OR, 1.3; 95% CI, 1.1–1.6] was observed in IVF/ICSI compared with spontaneous conception.Conclusion(s): When differentiating between order and mode of conception, it seems that assisted reproductive technology plays a role in mean birth weight and risk of low birth weight and preterm birth. Birth weight was higher in siblings born after FER compared with fresh embryos replacement.

Hemorheologic profile in healthy women undergoing controlled ovarian stimulation - Corrected Proof

2010-09-02

We investigated the hemorheologic profile in 110 women undergoing controlled ovarian stimulation and provide evidence that smokers and women with body mass index >25 kg/m2 exhibit alterations of rheologic profile. A progressive increase of whole-blood viscosity throughout the ovarian stimulation cycle was observed; deformability and aggregation of erythrocytes decreased from baseline to the beginning of recombinant FSH administration, then remained unchanged throughout the next days; hematocrit mildly decreased during the last days of recombinant FSH administration; and fibrinogen and cholesterol levels decreased and increased, respectively, throughout the stimulation cycle.

Benefit of uterine artery ligation in laparoscopic myomectomy - Corrected Proof

Ji Hae Bae, Gun Oh Chong, Won Joon Seong, Dae Gy Hong, Yoon Soon Lee — 2010-09-02

Objective: To determine the impact of uterine artery ligation in laparoscopic myomectomy, according to surgical results and clinical outcomes.Design: Single-center, nonrandomized, comparative study.Setting: University hospital, tertiary referral center.Patient(s): Ninety women undergoing laparoscopic myomectomy.Intervention(s): Laparoscopic myomectomy with or without uterine artery ligation.Main Outcome Measure(s): Surgical results and clinical outcomes.Result(s): Fifty-one patients (56.6%) underwent laparoscopic myomectomy with uterine artery ligation (group A), and 39 patients (43.3%) underwent laparoscopic myomectomy alone (group B). The mean operating time was 100.0 ± 33.8 minutes in group A and 90.0 ± 37.1 minutes in group B. Both groups were similar with respect to mean blood loss (72.3 ± 109.0 mL vs. 62.6 ± 77.3 mL). The myoma recurrence rate in group A was significantly less than in group B after a median follow-up period of 11.1 months (2% vs. 13%).Conclusion(s): Both groups were similar with respect to surgical results. However, the recurrence rate was significantly lower in group A compared with group B.

Peroxisome proliferator-activated receptor gamma and early folliculogenesis during an acute hyperandrogenism condition - Corrected Proof

2010-09-02

Acute hyperandrogenism decreases serum P levels and induces early apoptosis of antral follicles by a mechanism mediated by the peroxisome proliferator-activated receptor gamma system and independent of the steroidogenic acute regulator protein.

Erratum - Corrected Proof

2010-09-02

The authors of Genome-based expression profiling as a single standardized microarray platform for the diagnosis of endometrial disorder: an array of 126-gene model (Fertil Steril. 2010;94:114–119) would like to clarify that they did not perform microarray experiments themselves in Chang Gung Memorial Hospital. Instead, the source of data is the publicly accessible Gene Expression Omnibus (GEO), and the dataset is deposited to GEO with the accession number GSE4888. The description of RNA extraction and microarray experiments was meant only to help readers quickly realize the laboratory procedures. The authors are grateful for the original researchers, Talbi et al. (cited as reference 1), for the use of their deposited microarray datasets in this article.

Erratum - Corrected Proof

2010-09-02

The authors of Change of proinflammatory cytokines follows certain patterns after induction of endometriosis in a mouse model (Fertil Steril 2010;93:1448–54) inadvertently included the wrong image in Figure 1F. The correct image is provided in the amended Figure 1 below.

International Federation of Fertility Societies Surveillance 2010: preface - Corrected Proof

Howard W. Jones, Ian Cooke, Roger Kempers, Peter Brinsden, Doug Saunders — 2010-09-02

Surveillance is a triennial worldwide compendium of national rules and regulations for assisted reproductive technology. It was last published in 2007.

Day 2 versus day 3 embryo transfer in poor responders: a prospective randomized trial - Corrected Proof

2010-09-01

Day 2 embryo transfer has been suggested as a method to improve pregnancy rates in poor responders compared with day 3 transfer. Our prospective randomized controlled trial does not show a difference in outcomes based on day of embryo transfer.

Microdose gonadotropin-releasing hormone agonist in the absence of exogenous gonadotropins is not sufficient to induce multiple follicle development - Corrected Proof

2010-09-01

Because the effectiveness of the “microdose flare” stimulation protocol often is attributed to the dramatic endogenous gonadotropin release induced by the GnRH agonist, the aim of this study was to determine whether use of microdose GnRH agonist alone could induce multiple ovarian follicle development in normal responders. Based on these data, the duration of gonadotropin rise is approximately 24 to 48 hours and is too brief to sustain continued multiple follicle growth.

Age at onset of multiple sclerosis is correlated to use of combined oral contraceptives and childbirth before diagnosis - Corrected Proof

Per Holmqvist, Mats Hammar, Anne-Marie Landtblom, Jan Brynhildsen — 2010-08-31

The aim of this study was to evaluate whether age of onset of multiple sclerosis is related to use of combined oral contraceptives and/or timing of childbirth. The results showed that use of combined oral contraceptives and childbirth before the first multiple sclerosis symptom was correlated to a higher mean age at the onset of the disease.

Which are the ideal donor and recipient vessels for a whole ovarian transplantation? - Corrected Proof

Stéphane Ploteau, Jean-Michel Rogez, Jacques Donnez, Benoît Lengelé — 2010-08-31

Objective: To compare deep circumflex iliac (DCI) and deep inferior epigastric (DIE) pedicles as potential recipient vessels for a whole ovarian microvascular transplantation.Design: Anatomical study.Setting: Laboratory of anatomy, university center.Patient(s): Ten fresh human female cadavers.Intervention(s): Anatomical dissections, vascular injections, histologic analysis.Main Outcome Measure(s): Morphological analysis of the gonadic, DCI, and DIE pedicles; diameter of the vessels at regular intervals along their entire length. Comparisons of the caliber values between receiving (DCI and DIE) and gonadic pedicles aiming to determine the optimal size match.Result(s): We highlight a tortuous appearance of the gonadic artery. This morphology contrasted with the venous system that included two or three straight veins, one of them being wider than the others. The gonadic vessels converge into a wider artery and vein at 5 cm from the ovary. An optimal size match existed between gonadic and DCI arteries and veins sections, in 13 of 14 gonadic pedicles.Conclusion(s): A safe microsurgical whole ovarian transplantation is feasible if the gonadic pedicle is harvested with a minimal length of 5 cm from the ovary. The DCI pedicle seems to have the best size match with the ovarian vessels to perform a reliable end-to-end microvascular anastomosis.

Periodontal disease in polycystic ovary syndrome - Corrected Proof

2010-08-31

Polycystic ovary syndrome (PCOS) and periodontal disease (inflammatory diseases of the tissues around teeth) are common disorders associated with diabetes and cardiometabolic risk. Comprehensively examining the periodontal status in PCOS, this study suggests that the susceptibility for periodontal disease may significantly increase in patients with PCOS compared with healthy young women, and that local/periodontal oxidant status appears to be affected in PCOS.

Biological predictive criteria for clinical pregnancy after elective single embryo transfer - Corrected Proof

2010-08-31

In this prospective observational study, the onset of a clinical pregnancy after elective single embryo transfer (eSET) was significantly associated with: 1) the woman's age as well as the number of good- and top-quality embryos; and 2) the day of the embryo transfer (day 3 > day 2). Good-quality embryos had the same ability to implant, regardless of the zygotic score, the day 1 early cleavage rate, the fragmentation degree, and the top-quality assessment, specifying the eligibility criteria for eSET.

The effect of air bubble position after blastocyst transfer on pregnancy rates in IVF cycles - Corrected Proof

2010-08-31

Objective: To investigate the relationship between air bubble position after blastocyst transfer (BT) and pregnancy rates (PRs).Design: Retrospective cohort study.Setting: University-based infertility center.Patient(s): Three hundred fifteen consecutive nondonor BTs by a single provider.Intervention(s): Catheters were loaded with 25 μL of culture media, 20 μL of air, 25 μL of media containing the blastocysts, 20 μL of air, and a small amount of additional media. The distance from the air bubble to the fundus, as seen on abdominal ultrasound examination, was measured at the time of transfer. Air bubble location was categorized as <10 mm, 10–20 mm, and >20 mm from the fundus.Main Outcome Measure(s): Clinical pregnancy rate.Result(s): After controlling for age, parity, FSH and frozen transfers, and accounting for repeated cycles per patient, the PRs for both the >20-mm (38.3%) and the 10–20-mm (42.0%) from the fundus group were significantly reduced compared with the group in which the bubble was <10 mm from the fundus (62.5%).Conclusion(s): This study is the first to suggest that BT closer to the fundus is associated with higher PR. Although no ectopic pregnancies occurred in the <10-mm group, this outcome should be monitored closely in larger studies.

SEPT12 deficiency causes sperm nucleus damage and developmental arrest of preimplantation embryos - Corrected Proof

2010-08-31

Oocytes fertilized with spermatozoa obtained from Septin 12+/– chimeric mice failed to develop beyond the morula stage after IVF and intracytoplasmic sperm injection because of significant DNA defects in the spermatozoa. Given that SEPT12 is expressed at the edge of the sperm nucleus in both humans and mice, we hypothesized the vital roles of Septin 12 in sperm head shaping, nuclear DNA condensation, and early embryonic development.

Detection of Hodgkin lymphoma within ovarian tissue - Corrected Proof

2010-08-31

Objective: To describe the detection of Hodgkin lymphoma within ovarian tissue taken at the time of harvest for cryopreservation.Design: Case report.Setting: University-affiliated women's hospital.Patient(s): A 19-year-old woman diagnosed with Hodgkin lymphoma.Intervention(s): Laparoscopic removal of ovarian tissue for cryopreservation.Main Outcome Measure(s): Histologic and immunohistochemical evaluation of ovarian tissue harvested for fertility preservation.Result(s): Histologic and immunohistochemical identification of Hodgkin lymphoma within ovarian tissue harvested for cryopreservation.Conclusion(s): Ovarian cryopreservation and subsequent autografting is a procedure still in an experimental phase that has yielded promising findings. This option is frequently offered to young women with neoplasms such as Hodgkin lymphoma. Although the risk of Hodgkin lymphoma infiltration into the ovary may be low, the identification of lymphoma in this case emphasizes the importance of histologic examination of ovarian tissue before freezing and indicates that there is a possibility of reintroducing tumor.

Four spontaneous pregnancies and three live births following subcutaneous transplantation of frozen banked ovarian tissue: What is the explanation? - Corrected Proof

Kutluk Oktay, Ilgın Türkçüoğlu, Kenny A. Rodriguez-Wallberg — 2010-08-31

Objective: To report the long-term follow-up of an experimental heterotopic ovarian transplantation with frozen-thawed ovarian tissue.Design: Long-term follow-up of an experimental surgery; case report.Setting: Academic reproductive medicine center.Patient(s): A 28-year-old cancer survivor with previous Hodgkin disease and relapse.Intervention(s): Laparoscopic oophorectomy for ovarian cryopreservation before preconditioning chemotherapy for hematologic stem cell transplantation. Ovarian tissue thawing and subcutaneous heterotopic ovarian transplantation in the lower abdominal wall 2½ years after the hematologic stem cell transplantation.Main Outcome Measure(s): Resumption of ovarian function after transplantation, recovery of fertility, and pregnancy outcome.Result(s): Follicle development was observed in the graft 2 months after transplantation, and a P value of 14 ng/mL indicated ovulation. The patient conceived spontaneously four times within 5 years and delivered three children. The in situ ovary remained atrophic but showed occasional follicle activity contemporaneously with the graft.Conclusion(s): The mechanism behind spontaneous restoration of fertility with consecutive viable pregnancies after a heterotopic ovarian transplantation needs to be explored. Further laboratory and clinical research will be needed to explore the true origin of pregnancies after ovarian transplantations.

GnRH-agonist induced depressive and anxiety symptoms during in vitro fertilization–embryo transfer cycles - Corrected Proof

2010-08-31

To determine whether the use of a GnRH agonist inducing a hypogonadic state during IVF-ET cycles induces negative mood symptoms, we conducted a prospective randomized study in 108 women comparing two different controlled ovarian stimulation protocols. A significant phase effect was observed for depression and anxiety symptoms during IVF-ET cycles reflecting an increase in symptoms between the hypogonadal phase and the peak in gonadotropin stimulation; however, the hypogonadal phase induced by the GnRH agonist was not associated with a significant increase in any of the studied mood parameters.

Cetrorelix lowers premature luteinization rate in gonadotropin ovulation induction–intrauterine insemination cycles: a randomized-controlled clinical trial - Corrected Proof

2010-08-31

Attempting to compare the rates of premature luteinization (PL), clinical pregnancy, and cycle cancellation in ovulation induction–intrauterine insemination (OI-IUI) cycles with and without the GnRH antagonist, cetrorelix, a randomized-controlled trial was undertaken in which patients were randomized to one of two OI-IUI protocols. Those in the cetrorelix arm showed a significantly reduced rate of PL and no change in clinical pregnancy or cycle cancellation rate, leading to the conclusion that GnRH antagonists can decrease the rate of PL, but appear to have no effect on pregnancy or cycle cancellation in gonadotropin OI-IUI cycles.

The effect of transdermal testosterone gel pretreatment on controlled ovarian stimulation and IVF outcome in low responders - Corrected Proof

Chung-Hoon Kim, Colin M. Howles, Hyang-Ah Lee — 2010-08-31

Objective: To investigate the effectiveness of treatment with transdermal testosterone gel (TTG) before controlled ovarian stimulation (COS) using GnRH antagonist multiple-dose protocol (MDP) in low responders undergoing IVF/intracytoplasmic sperm injection (ICSI).Design: Prospective randomized controlled trial.Setting: University-affiliated infertility clinic.Patient(s): A total of 110 low responders, who were defined as patients who failed to produce ≤3 follicles with a mean diameter of ≥16 mm with the result that ≤3 oocytes were retrieved despite the use of a high gonadotropin dose (>2,500 IU) in a previous failed IVF/ICSI cycle.Intervention(s): Patients were randomized into TTG pretreatment group or control group. For TTG pretreatment group, 12.5 mg TTG were applied daily for 21 days in the cycle preceding COS for IVF.Main Outcome Measure(s): COS results and IVF outcome.Result(s): There were no differences in patients’ characteristics between the two groups. Total dose and days of rhFSH used were significantly fewer in the TTG pretreatment group than in the control group. The numbers of oocytes retrieved, mature oocytes, fertilized oocytes, and good-quality embryos were significantly higher in the TTG pretreatment group. Embryo implantation rate and clinical pregnancy rate per cycle initiated also were significantly higher in the women pretreated with TTG. No patient reported adverse effects attributed to TTG use.Conclusion(s): TTG pretreatment might be beneficial in improving both response to COS and IVF outcome in low responders undergoing IVF/ICSI.

Evaluation of endometrial biomarkers for semi-invasive diagnosis of endometriosis - Corrected Proof

2010-08-27

Objective: To test the hypothesis that specific proteins and peptides are expressed differentially in eutopic endometrium of women with and without endometriosis and at specific stages of the disease (minimal, mild, moderate, or severe) during the secretory phase.Design: Patients with endometriosis were compared with controls.Setting: University hospital.Patient(s): A total of 29 patients during the secretory phase were selected for this study on the basis of cycle phase and presence or absence of endometriosis.Intervention(s): Endometriosis was confirmed laparoscopically and histologically in 19 patients with endometriosis of revised American Society for Reproductive Medicine stages (9 minimal-mild and 10 moderate-severe), and the presence of a normal pelvis was documented by laparoscopy in 10 controls.Main Outcome Measure(s): Protein expression of endometrium was evaluated with use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. The differential expression of protein mass peaks was analyzed with use of support vector machine algorithms and logistic regression models.Result(s): Data preprocessing resulted in differential expression of 73, 30, and 131 mass peaks between controls and patients with endometriosis (all stages), with minimal-mild endometriosis, and with moderate-severe endometriosis, respectively. Endometriosis was diagnosed with high sensitivity (89.5%) and specificity (90%) with use of five down-regulated mass peaks (1.949 kDa, 5.183 kDa, 8.650 kDa, 8.659 kDa, and 13.910 kDa) obtained after support vector machine ranking and logistic regression classification. With use of a similar analysis, minimal-mild endometriosis was diagnosed with four mass peaks (two up-regulated: 35.956 kDa and 90.675 kDa and two down-regulated: 1.924 kDa and 2.504 kDa) with maximal sensitivity (100%) and specificity (100%). The 90.675-kDa and 35.956-kDa mass peaks were identified as T-plastin and annexin V, respectively.Conclusion(s): Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry analysis of secretory phase endometrium combined with bioinformatics puts forward a prospective panel of potential biomarkers with sensitivity of 100% and specificity of 100% for the diagnosis of minimal to mild endometriosis.

Antimullerian hormone serum levels predict response to controlled ovarian hyperstimulation but not embryo quality or pregnancy outcome in oocyte donation - Corrected Proof

2010-08-26

The objective of this retrospective cross-sectional study was to evaluate the value of basal serum antimullerian hormone (AMH) levels as a predictor of ovarian response and pregnancy outcome in a donor egg program. The study showed that AMH was superior to other biomarkers of ovarian reserve in predicting low and high response in young women selected as oocyte donors, but that it was not predictive of embryo morphology or pregnancy outcome in the recipient population.

Long-term urinary retention after laparoscopic surgery for deep endometriosis - Corrected Proof

2010-08-26

Objective: To report on chronic urinary retention after surgery for deep endometriosis and the possible risk factors for this complication.Design: Descriptive study.Setting: University hospital.Patient(s): Four patients with deep endometriosis who developed this complication.Intervention(s): Laparoscopic surgery, intermittent self-catheterization (ISC).Main Outcome Measure(s): To identify site(s) of lesion associated with this complication.Result(s): Four patients developed this complication from damage to the inferior hypogastric plexus involving the sympathetic and/or parasympathetic afferents from the bladder. One patient regained complete bladder function 8 months after surgery, and the others required ISC at the time of writing (13, 24, and 3 months after surgery). Patients with lesions located laterally and deep in the uterosacral ligaments especially near the ischial spines were at high risk. All patients were, however, satisfied with the results of surgery.Conclusion(s): Most such injuries are unpredictable, but in our experience, two of three patients with lesions near the ischial spine developed this complication. Chronic urinary retention after radical endometriosis surgery is rare and often under reported. Although most lesions are unilateral and have a potential for improvement, it is not known how long these effects will last. More data from other centers may help in providing additional information.

A sperm viability test using SYBR-14/propidium iodide flow cytometry as a tool for rapid screening of primary ciliary dyskinesia patients and for choosing sperm sources for intracytoplasmic sperm injection - Corrected Proof

2010-08-26

Spermatozoa viability tests based on dual-color flow cytometry after staining with Sybr-14/propidium iodide were performed on 44 men with complete asthenospermia for primary ciliary dyskinesia (PCD) screening, and seven were identified with PCD by electron microscopy of ultrastructural ciliary defects. Six PCD patients underwent eight intracytoplasmic sperm injection therapy cycles using ejaculated sperm or testicular sperm, obtaining a mean fertilization rate of 46.6%, with three healthy babies born and one in utero at the time of writing.

Functional association of interleukin-18 gene –607 C/A promoter polymorphisms with endometriosis - Corrected Proof

Lokman Ayaz, Sevim Karakaş Çelik, Filiz Çayan, Nurcan Aras-Ateş, Lülüfer Tamer — 2010-08-26

This study evaluated for the first time the relationship between interleukin-18 (IL-18) C607A genotypes and endometriosis in 135 women with endometriosis and 84 controls. In the study population, IL-18 –607∗A homozygote and A allele were positively correlated with the risk of developing endometriosis or the stage of endometriosis.

Activation of adenosine A2A receptors by polydeoxyribonucletide increases vascular endothelial growth factor and protects against testicular damage induced by experimental varicocele in rats - Corrected Proof

2010-08-26

In rat experimental varicocele, polydeoxyribonucleotide (PDRN) induces vascular endothelial growth factor (VEGF) production, thereby enhancing testicular function. This may point to a new therapeutic approach in human varicocele.

Comprehensive embryo analysis of advanced maternal age–related aneuploidies and mosaicism by short comparative genomic hybridization - Corrected Proof

2010-08-26

The short comparative genomic hybridization (short-CGH) method was used to perform a comprehensive cytogenetic study of isolated blastomeres from advanced maternal age embryos, discarded after fluorescent in situ hybridization (FISH) preimplantation genetic screening (PGS), detecting aneuploidies (38.5% of which corresponded to chromosomes not screened by 9-chromosome FISH), structural aberrations (31.8%), and mosaicism (77.3%). The short-CGH method was subsequently applied in one PGS, achieving a twin pregnancy.

Failed IVF cycles and the risk of subsequent preeclampsia or fetal growth restriction: a case-control exploratory study - Corrected Proof

2010-08-26

Objective: To investigate the hypothesis that women achieving pregnancy after two or more failed embryo transfers (ETs) of good quality embryos have increased incidence of preeclamptic toxemia (PET) or fetal growth restriction (FGR) compared with those conceiving in the first ET after in vitro fertilization (IVF).Design: Case-control study.Setting: Tertiary infertility center.Patient(s): Women who underwent IVF at the St. Mary's Hospital, Manchester, between January 2000 and June 2008 and conceived in the first ET, versus those who conceived after two or more failed ETs.Intervention(s): Retrospective case-note review.Main Outcome Measure(s): Incidence of PET or FGR.Result(s): Case notes of 364 eligible patients were identified: 125 conceived after two or more failed ETs and 239 in the first ET. The incidence of the primary outcome (PET or FGR) for the total number of pregnancies showed no significant difference between cases and controls (age and multiplicity adjusted odds ratio 1.2, 95% confidence interval 0.5–3.0). There were no significant differences between case and control subjects for the secondary outcomes.Conclusion(s): This study failed to demonstrate that women conceiving after two or more unsuccessful ETs are at increased risk of PET or FGR. More studies are required to investigate the relationship further.

The typical ovarian endometrioma has a surface origin - Corrected Proof

Ivo Brosens — 2010-08-26

To the Editor: Whereas the complexity of the ovarian endometrioma is well appreciated, reconstructive surgery may differ according to the pathogenesis. Resected cysts are useful for confirmation of the diagnosis, but fail to demonstrate the structure and pathogenesis of the endometrioma. Few authors, however, have studied the ovarian endometrioma in situ. In a detailed study of 29 ovary specimens with the endometrioma in situ, Hughesdon found that, in all but three cases, the endometrioma was a pseudocyst with an essentially similar structure: the ovary was adherent to the posterior side of the parametrium, the inside of the cyst was constituted by invaginated ovarian cortex, endometriosis was found at the site of adhesion, and a thin layer of superficial endometrial-like tissue extended to cover partially or fully the invaginated cortex.

Reply of the Authors - Corrected Proof

Jacques Donnez — 2010-08-26

We were interested to read the letter of Ivo Brosens, and we agree that the typical ovarian endometrioma has a surface origin. However, we disagree with Hughesdon's theory . Indeed, we strongly believe that ovarian endometriomas are caused by metaplasia of invaginated coelomic epithelium that covers the ovarian surface.

Luteal phase estradiol versus luteal phase estradiol and antagonist protocol for controlled ovarian stimulation before in vitro fertilization in poor responders - Corrected Proof

2010-08-26

Luteal phase synchronization of follicular growth has been suggested as a means to improve ovarian response in low responders. We compared luteal E2 and antagonist (n = 256) with luteal E2 only (n = 57) before antagonist protocol in low responders. The addition of GnRH antagonist to luteal E2 for luteal suppression before ovarian stimulation for IVF does not improve IVF outcomes in poor responders.

Increased plasma levels of phthalate esters in women with advanced-stage endometriosis: a prospective case-control study - Corrected Proof

2010-08-26

We performed the present prospective case-control study to evaluate whether the plasma concentrations of phthalate esters are elevated in women with advanced-stage endometriosis in a Korean population. Measuring plasma levels of monoethylhexyl phthalate and di-(2-ethylhexyl) phthalate in 97 women with advanced-stage endometriosis and 169 control women by liquid chromatography–tandem mass spectrometry, we found that the concentrations of monoethylhexyl phthalate, as well as di-(2-ethylhexyl) phthalate, are significantly higher in those with advanced-stage endometriosis, which supports the hypothesis that exposure to phthalate might play a role in the establishment of endometriosis.

Endometriosis and autoimmune disease: association of susceptibility to moderate/severe endometriosis with CCL21 and HLA-DRB1 - Corrected Proof

2010-08-26

This study investigates the association of rheumatoid arthritis–associated single nucleotide polymorphisms in endometriosis. We found an association of CCL21 (rs2812378) and HLA-DRB1 (rs660895) with moderate to severe endometriosis.

Cyclooxygenase-2 network as predictive molecular marker for clinical pregnancy in in vitro fertilization - Corrected Proof

2010-08-26

The gene expression of human endometrium on the day of oocyte retrieval of pregnant and nonpregnant patients in a stimulated IVF cycle was compared in two independent groups with different GnRH-antagonist ovarian stimulation protocols. The present data suggest that increased gene expression of cyclooxygenase-2, together with the expression of other molecules in the cyclooxygenase-2 network, on the day of oocyte retrieval in GnRH-antagonist cycles coincides with a lower probability of achieving a clinical pregnancy in this cycle.

Recurrent aberrations identified by array-CGH in patients with Mayer-Rokitansky-Küster-Hauser syndrome - Corrected Proof

2010-08-26

Objective: To identify genetic causes of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome.Design: Prospective laboratory study.Setting: University hospital.Patient(s): Fifty-six patients with MRKH syndrome.Intervention(s): Identification of microdeletions and –duplications in a group of 48 MRKH patients by array-CGH. Results obtained by array-CGH were confirmed by RT-qPCR. Sequential analysis of two candidate genes LHX1 and HNF1B in a group of 56 MRKH patients.Main Outcome Measure(s): Identification of chromosomal regions and genes (recurrent and private) associated with MRKH syndrome.Result(s): We could delineate three definitively relevant regions (1q21.1, 17q12, and 22q11.21) and suggest that LHX1 und HNF1B are candidate genes for MRKH syndrome, because we identified recurrent deletions affecting these genes and a possible causative missense mutation in LHX1.Conclusion(s): Our findings suggest that different chromosomal regions are associated with MRKH syndrome.

Falloposcopic tuboplasty as an option for tubal infertility: an alternative to in vitro fertilization - Corrected Proof

Yudai Tanaka, Hiroto Tajima — 2010-08-26

This is a case series to evaluate the efficacy of falloposcopic tuboplasty (FT), a surgical technique of recanalization of occluded fallopian tube. Of 153 patients with tubal infertility for more than 2 years who underwent FT, 28.9% (44 patients) conceived, and 27.3%, 75.0%, and 88.8% conceived in 1 month, 6 months, and 12 months after FT, respectively.

Epistasis between CYP19A1 and ESR1 polymorphisms is associated with premature ovarian failure - Corrected Proof

Sunshin Kim, Jung-A Pyun, HyunJun Kang, JiHye Kim, Dong Hyun Cha, KyuBum Kwack — 2010-08-26

Because an interaction between CYP19A1 and ESR1 may play a key role in determining the level of circulating E2 by way of the hypothalamus-hypophysis-ovarian axis, the effect of single nucleotide polymorphism (SNP)–SNP interactions between CYP19A1 and ESR1 on the development of premature ovarian failure (POF) was investigated by comparing the polymorphisms of 98 patients with POF and 218 matched controls of Korean ethnicity. A significant association with POF risk was found for the combined genetic effect between the CYP19A1 3′untranslated region (UTR) SNP rs10046 (CT+TT) and the intronic ESR1 SNP rs1569788 (CC) genotype (odds ratio = 12.67, 95% confidence interval: 1.61–99.71), and a statistically significant association was also observed between POF and the CYP19A1 3′UTR SNP rs10046 under a dominant model (odds ratio = 2.51, 95% confidence interval: 1.33–4.76), suggesting that epistasis between ESR1 and CYP19A1 may be involved in the regulation of folliculogenesis.

Age-specific nomogram for the decline in antral follicle count throughout the reproductive period - Corrected Proof

2010-08-26

Objective: To investigate the relationship between antral follicle count (AFC) and chronological age and to establish normal values for AFC in women with regular menstrual cycles.Design: Cross-sectional study.Setting: University hospital.Patient(s): Four hundred fifteen premenopausal women were recruited for the study. Data from 362 patients were available for the statistical analysis.Intervention(s): AFC was measured by transvaginal ultrasound examination.Main Outcome Measure(s): Estimating the relationship between AFC and age and developing the AFC nomogram.Result(s): The analysis showed a linear decline in AFC with age; for every year increase in age, the median AFC decreases by 0.4. The AFC corresponding to the 5th, 25th, 50th, 75th, and 95th centiles for each age have been calculated.Conclusion(s): A linear relationship of AFC to age was found. For the first time, a nomogram reporting normal and interquartile values for AFC, age by age, throughout the reproductive period has been provided. Until now, the interpretation of the measurement was mainly based on the individual experience of the operator, because no normative data were present. Therefore, the establishment of a nomogram of AFC values is the first step to counsel patients on a scientific basis.

Reply of the Authors: - Corrected Proof

Si-Ming Wei, Zhi-Zhong Yan, Jian Zhou — 2010-08-26

Testicular torsion is a common urologic emergency. Surgical detorsion is currently the only treatment for testicular torsion. It seems that the main pathophysiology of testicular torsion–detorsion is ischemia–reperfusion injury of the testis. Testicular ischemia–reperfusion injury is associated with overgeneration of reactive oxygen species (ROS), such as superoxide anions, hydrogen peroxide, hydroxyl radicals, and nitric oxide. Reactive oxygen species inflict significant injury on ischemic tissue through oxidation of cell membrane lipids, protein, and DNA.

Molecular mechanisms for curcumin benefits against ischemic injury - Corrected Proof

Amirhossein Sahebkar — 2010-08-26

To the Editor: Curcumin (diferuloylmethane) is the yellow bioactive pigment from the powdered dry rhizomes of Curcuma longa Linn. (commonly known as turmeric) . Heretofore, numerous biological targets and pharmacologic activities have been reported for curcumin, thereby posing this polyphenol as a promising therapeutic agent against a wide variety of disorders. A number of studies have reported protective effects of this polyphenol in reducing ischemia–reperfusion (I/R) injury in several tissues. Among these is the recent interesting study reported by Wei et al. . In the mentioned study, the authors demonstrated the protective effect of curcumin on testicular I/R injury. On the basis of their findings, the authors proposed that the protective effects of curcumin could be due to its beneficial impacts on the formation and scavenging of reactive oxygen species (ROS), as well as induction of heme oxygenase-1. Herewith, I would like to propose four other potential mechanisms by which curcumin may exert its protective effects against I/R injury.

Improving fertility preservation in cancer: ovarian tissue cryobanking followed by ovarian stimulation can be efficiently combined - Corrected Proof

2010-08-26

This pilot study evaluated whether combination of partial removal of ovarian tissue for cryobanking followed by ovarian stimulation and cryopreservation of oocytes can improve the efficacy of fertility preservation without further delaying cancer treatment. Initial partial removal of ovarian tissue did not substantially affect the average number and quality of retrieved oocytes after ovarian stimulation in this study.

Low-dose estrogen and drospirenone combination: effects on glycoinsulinemic metabolism and other cardiovascular risk factors in healthy postmenopausal women - Corrected Proof

2010-08-23

Objective: To evaluate the effects of a daily E2 (1 mg) plus drospirenone oral formulation (2 mg) on glycoinsulinemic metabolism, lipid profile, and endothelial function in symptomatic healthy menopausal women.Design: Randomized, double-blind study.Setting: Operative Division of Endocrinological Gynecology, Catholic University of the Sacred Heart, Rome, Italy.Patient(s): Forty postmenopausal women.Intervention(s): Patients were randomly submitted to receive treatment with an oral dose of E2 (1 mg) plus drospirenone (2 mg) (group A) or placebo (group B).Main Outcome Measure(s): Hormonal and lipid assessment; evaluation of glucose and insulin metabolism by the clamp test and the oral glucose tolerance test; evaluation of endothelial function by the vascular reactivity test.Result(s): Total cholesterol levels, low-density lipoprotein cholesterol levels, and nonesterified fatty acids levels significantly decreased both after 3 and 6 months. No changes in high-density lipoprotein, triglycerides, apolipoprotein A1, apolipoprotein B, and lipoprotein (a) were found. Treatment resulted in few changes in glycoinsulinemic metabolism. We observed a significant reduction of the area under curve of insulin after 6 months of therapy. Endothelial function was significantly influenced by treatment, and an improvement in both flow-mediated dilatation and nitrate-mediated dilatation values after 6 months was observed.Conclusion(s): Low-dose E2/drospirenone treatment did not reveal any negative effect on carbohydrate metabolism, acting in a neutral way on insulin sensitivity. The treatment induced favorable changes in lipid profile and showed a significant improvement of vascular reactivity.

Effectiveness of misoprostol for office hysteroscopy without anesthesia in infertile patients - Corrected Proof

2010-08-23

Objective: To evaluate and compare the effectiveness of oral and vaginal misoprostol versus placebo to facilitate office hysteroscopy without anesthesia during infertile diagnostic evaluation.Design: Randomized, prospective trial.Setting: Patients scheduled for diagnostic office hysteroscopy at a university hospital.Patient(s): Seventy-five infertile patients scheduled for diagnostic office hysteroscopy.Intervention(s): Patients were divided into three groups: group A received oral misoprostol 600 μg; group B, vaginal misoprostol 400 μg; and group C, oral placebo.Main Outcome Measure(s): Pain, evaluated by visual analogue scale, and surgical time were recorded and compared. Statistical analysis was done using Student's t-test.Result(s): Pain was low in the vaginal misoprostol group. Mean visual analogue scale in the oral misoprostol group was 6.04 ± 1.5; in the vaginal misoprostol group 2.85 ± 1.2; and in the placebo group 7.50 ± 1.5. Procedural time for office hysteroscopy was shorter in the vaginal misoprostol group (2.7 ± 1.0 minutes) compared with group A (5.5 ± 1.1 minutes) and group C (6.3 ± 3.8 minutes).Conclusion(s): Vaginal misoprostol, 400 μg, administered the day before office hysteroscopy considerably reduces pain and the time needed for hysteroscopy. This simple strategy may facilitate office hysteroscopy during an infertility work-up.

Clinical complications after transvaginal oocyte retrieval in 7,098 IVF cycles - Corrected Proof

2010-08-20

We report the complications observed after transvaginal oocyte retrieval guided by ultrasound in 7,098 IVF cycles. The frequency of severe complications in our patients was 0.08%, of which four cases were intraperitoneal bleeding (0.06%) and two were cases of ovarian abscess (0.003%).

Levonorgestrel-releasing intrauterine system (LNG-IUS) as an effective treatment option for endometrial hyperplasia: a 15-year follow-up study - Corrected Proof

2010-08-19

The levonorgestrel-releasing intrauterine system may represent an effective treatment option in >85% of endometrial hyperplasia cases, but histologic regression during and/or at the end of treatment does not assure stable recovery. We recommend periodic endometrial samplings for at least the first 2 years of follow-up and long-term clinical surveillance thereafter.

In combined first-trimester Down syndrome screening, the false-positive rate is not higher in pregnancies conceived after assisted reproduction compared with spontaneous pregnancies - Corrected Proof

2010-08-19

The maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) were reduced in hormonally stimulated pregnancies in the in vitro fertilization and intracytoplasmic sperm injection groups (N = 176; PAPP-A: 0.82) and in the entire assisted reproduction group (N = 282; PAPP-A: 0.83) as compared with controls (N = 24,783; PAPP-A: 0.94). However, the false-positive rate of first-trimester combined screenings was not statistically significantly increased in assisted reproduction pregnancies after adjustment for maternal age.

Clinical relevance of sperm DNA assessment: an update - Corrected Proof

Christopher L.R. Barratt, Christopher J. De Jonge — 2010-08-19

For sperm DNA assessments to be widespread effective clinical tools, key objectives need to be urgently achieved. These include robust standardized methods, systems for training staff and ongoing quality control; and rigorous examination of the clinical outcomes. We discuss the significance of these objectives and conclude that, if achieved, the clinical utility of DNA damage assessment will be fully realized.

Progesterone receptor gene polymorphisms and risk of endometriosis: results from an international collaborative effort - Corrected Proof

2010-08-18

Objective: To investigate the association between self-reported endometriosis and the putative functional promoter +331C/T single nucleotide polymorphism and the PROGINS allele.Design: Control subjects from ovarian cancer case-control studies participating in the international Ovarian Cancer Association Consortium. The majority of controls are drawn from population-based studies.Setting: An international ovarian cancer consortium including studies from Australia, Europe, and the United States.Patient(s): Five thousand eight hundred twelve white female controls, of whom 348 had endometriosis, from eight ovarian cancer case-control studies.Intervention(s): None.Main Outcome Measure(s): Genotypes for the +331C/T single nucleotide polymorphism and PROGINS allele and a history of endometriosis.Result(s): The occurrence of endometriosis was reduced in women carrying one or more copies of the +331 T allele (odds ratio = 0.65; 95% confidence interval: 0.43–0.98), whereas there was no association between the PROGINS allele and endometriosis (odds ratio = 0.94, 95% confidence interval 0.76–1.16).Conclusion(s): Additional studies of the +331C/T variant are warranted given the current finding and the equivocal results of previous studies. The +331 T allele has been shown to result in a reduced progesterone (P) receptor A to P receptor B ratio, and if the observed association with endometriosis is confirmed it would suggest that this ratio is important for this disease.

Methylation patterns of Brahma during spermatogenesis and oogenesis: potential implications - Corrected Proof

2010-08-18

To compare methylation profiles and expression levels of Brahma at different stages of spermatogenesis, and to identify the methylation pattern during oogenesis, we analyzed gene expression and methylation patterns in murine germ cells at various developmental stages. The methylation levels of CpG islands within Brahma increased during spermatogenesis and decreased during oogenesis. This change in methylation pattern correlates with the change in expression of Brahma during spermatogenesis. As the degree of methylation increases, the expression decreases. The change in methylation is opposite during oogenesis, which suggests opposite expression levels.

Five mutations of mitochondrial DNA polymerase-gamma (POLG) are not a prevalent etiology for spontaneous 46,XX primary ovarian insufficiency - Corrected Proof

2010-08-11

The study objective was to determine if mutations in mitochondrial DNA polymerase gamma (POLG) are associated with spontaneous 46,XX primary ovarian insufficiency (sPOI) using restriction fragment length polymorphism analysis of genomic DNA. Of 201 women with 46,XX sPOI analyzed, we found only one case (0.5%, 95% confidence interval 0-3%) of heterozygosity for a POLG mutation, suggesting that this is not a common genetic etiology for this form of infertility.