Fertility and Sterility - Articles in Press

Integration of immunodeficiency virus in oocytes via intracytoplasmic injection: possible but extremely unlikely - Corrected Proof

2012-05-14

Objective: To determine if human oocytes can be infected with HIV-1 via intracytoplasmic injection and to determine the infection threshold.Design: Twenty-eight donated immature and unfertilized human oocytes from HIV-negative women were injected with 4 × 104 HIV-1 virions and 13 oocytes were used as uninjected controls. To determine the infection threshold, 543 cat oocytes were injected with 4 × 104, 4 × 102, or 40 copies of feline immunodeficiency virus (FIV) and 376 oocytes were used as controls.Setting: Academic hospital.Patient(s)/Animal(s): Donated immature human oocytes and mature cat oocytes.Intervention(s): Injection with HIV-1 or FIV.Main Outcome Measure(s): Viral integration as measured by fluorescent in situ hybridization with HIV-1-specific probes or by nested FIV polymerase chain reaction.Result(s): We detected viral integration in three of 28 (11%) human oocytes injected with 4 × 104 copies of HIV-1. When injected with high dose FIV (4 × 104 copies) 16%–49% of cat oocytes showed viral integration. This decreased to 2%–7% and 0.6%–1.8% when an intermediate (4 × 102 copies) or low (40 copies) dose was injected, respectively.Conclusion(s): Human and cat oocytes can be infected with HIV-1 and FIV respectively, when injected with high amounts of virus. The probability of viral integration is extremely low when small amounts of virus particles are injected. Taking into account the small volume injected during intracytoplasmic injection, the chances of viral integration are 0.00002%.

Pregnancies following ultrasound-guided drainage of tubo-ovarian abscess - Corrected Proof

2012-05-14

Objective: To study fertility among women treated by means of ultrasound-guided drainage and antibiotics for tubo-ovarian abscess (TOA).Design: Retrospective cohort study.Setting: A tertiary referral center.Patient(s): One hundred women of reproductive age treated for TOA between June 1986 and July 2003.Intervention(s): Transvaginal ultrasound-guided drainage of TOA was performed in all patients. The procedure was repeated if a substantial amount of pus was seen using ultrasonography 2–5 days after the initial aspiration, and repeated later if necessary.Main Outcome Measure(s): Frequency of naturally conceived pregnancies.Result(s): Twenty of 38 (52.6%; 95% CI 36.5–68.9%) women who intended to have a child achieved pregnancy naturally and became mothers. In addition, 7 (50%) of 14 women who were not on birth control on a regular basis became pregnant. No ectopic pregnancies were registered.Conclusion(s): Ultrasound-guided drainage of TOA in combination with antibiotics seems to preserve fertility in approximately half of the patients.

2-Methoxyestradiol causes functional repression of transforming growth factor β3 signaling by ameliorating Smad and non-Smad signaling pathways in immortalized uterine fibroid cells - Corrected Proof

Salama A. Salama, Concepcion R. Diaz-Arrastia, Gokhan S. Kilic, Marwa W. Kamel — 2012-05-14

Objective: To investigate the effects and the mechanism of action of 2-methoxyestradiol (2ME2) on transforming growth factor (TGF) β3–induced profibrotic response in immortalized human uterine fibroid smooth muscle (huLM) cells.Design: Laboratory study.Setting: University research laboratory.Patients(s): Not applicable.Interventions(s): Not applicable.Main Outcome Measure(s): huLM cells were treated with TGF-β3 (5 ηg/mL) in the presence or absence of specific Smad3 inhibitor SIS3 (1 μmol/L), inhibitor of the PI3K/Akt (LY294002, 10 μmol/L), or 2ME2 (0.5 μmol/L), and the expression of collagen (Col) type I(αI), Col III(αI), plasminogen activator inhibitor (PAI) 1, connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) were determined by real-time reverse-transcription polymerase chain reaction and immunoblotting. The effect of 2ME2 on Smad-microtubule binding was evaluated by coimmunoprecipitation.Result(s): Our data revealed that TGF-β3–induced fibrogenic response in huLM is mediated by both Smad-dependent and Smad-independent PI3K/Akt/mTOR signaling pathways. 2ME2 abrogates TGF-β3–induced expression of Col I(αI), Col III(αI), PAI-1, CTGF, and α-SMA. Molecularly, 2ME2 ameliorates TGF-β3–induced Smad2/3 phosphorylation and nuclear translocation. In addition, 2ME2 inhibits TGF-β3–induced activation of the PI3K/Akt/mTOR pathway.Conclusion(s): TGF-β3–induced profibrotic response in fibroid cells is mediated by Smad-dependent and Smad-independent PI3K/Akt/mTOR pathways. 2ME2 inhibits TGF-β3 profibrotic effects in huLM cells by ameliorating both Smad-dependent and Smad-independent signaling pathways.

Management of a cervical heterotopic pregnancy presenting with first-trimester bleeding: case report and review of the literature - Corrected Proof

Vasiliki A. Moragianni, Benjamin D. Hamar, Colin McArdle, David A. Ryley — 2012-05-14

Objective: To report a rare case of a cervical heterotopic pregnancy resulting from intrauterine insemination (IUI) that presented with first-trimester bleeding.Design: Case report and literature review.Setting: Large university-affiliated infertility practice.Patient(s): A 40-year-old gravida 2 para 1 Asian woman at 7-3/7 weeks gestational age following clomiphene citrate/IUI for the treatment of secondary infertility presented with heavy vaginal bleeding for several days.Intervention(s): Transvaginal ultrasound on admission revealed a single live intrauterine pregnancy and a cervical gestational sac containing a nonviable embryo. The patient continued to have vaginal bleeding and 2 days later underwent removal of the cervical ectopic pregnancy tissue with ring forceps, as well as an ultrasound-guided intracervical Foley balloon and cerclage placement. The bleeding subsided, and 48 hours later the Foley and cerclage were removed.Main Outcome Measure(s): Pregnancy outcome.Result(s): The remainder of the pregnancy was uncomplicated and the patient had a full-term cesarean delivery for footling breech of a healthy male infant.Conclusion(s): Cervical heterotopic pregnancy is a very rare event that almost universally results from infertility treatment. We present a case where we were able to remove the cervical ectopic and tamponade the bleeding, thus preserving the intrauterine pregnancy for this subfertile couple, and we review the existing literature.

The effect of body mass index on the outcomes of first assisted reproductive technology cycles - Corrected Proof

Vasiliki A. Moragianni, Stephanie-Marie L. Jones, David A. Ryley — 2012-05-14

Objective: To provide assisted reproductive technology (ART) outcome rates per body mass index (BMI) category after controlling for potential confounders.Design: Retrospective cohort study.Setting: Large university-affiliated infertility practice.Patient(s): Women undergoing ART.Intervention(s): None.Main Outcome Measure(s): The primary outcome was live birth. Analyses were stratified according to BMI category and adjusted for potential confounders, including maternal and paternal age, baseline serum FSH, duration of gonadotropin stimulation, mean daily gonadotropin dose, peak serum E2, number of oocytes retrieved, use of intracytoplasmic sperm injection, embryo quality and number, transfer day, and number of embryos transferred.Result(s): We analyzed the first autologous fresh IVF or IVF-ICSI cycle of 4,609 patients. There were no differences in the rates of cycle cancellation, spontaneous abortion, biochemical and ectopic pregnancies, or multiple births. After adjusting for potential confounders, patients with BMI ≥30.0 kg/m2 had significantly decreased odds of implantation, clinical pregnancy, and live birth. The adjusted odds ratio (95% confidence interval [CI]) of live birth were 0.63 (0.47–0.85) for BMI 30.00–34.99, 0.39 (0.25–0.61) for BMI 35.00–39.99, and 0.32 (0.16–0.64) for BMI ≥40.0 compared with normal-weight cohorts.Conclusion(s): Obesity has a significant negative effect on ART outcomes. Patients with BMI >30 kg/m2 have up to 68% lower odds of having a live birth following their first ART cycle compared with women with BMI <30.

Changes in hormonal profile and seminal parameters with use of aromatase inhibitors in management of infertile men with low testosterone to estradiol ratios - Corrected Proof

2012-05-14

Objective: To compare the effects of 2.5 mg letrozole with those of 1 mg anastrazole daily on the hormonal and semen profiles of a subset of infertile men with low T/E2 ratios.Design: Prospective, nonrandomized study.Setting: Reproductive medicine clinic.Patient(s): The study group consisted of 29 infertile men with a low serum T/E2 ratio (<10).Intervention(s): Patients were divided into two groups. Group A included 15 patients treated with 2.5 mg letrozole orally once daily for 6 months, and Group B consisted of 14 patients treated with 1 mg anastrazole orally every day for 6 months.Main Outcome Measure(s): Hormonal evaluation included measurement of serum FSH, LH, PRL, T, and E2. In all sperm analyses pretreatment and posttreatment total motile sperm counts (ejaculate volume × concentration × motile fraction) were evaluated.Result(s): The use of aromatase inhibitors (either letrozole or anastrazole) in cases of infertile men with low T/E2 ratios improved both hormonal and semen parameters.Conclusion(s): This study suggests that some men with severe oligospermia, low T levels, and normal gonadotropin concentration may have a treatable endocrinopathy.

Sirt1 exerts anti-inflammatory effects and promotes steroidogenesis in Leydig cells - Corrected Proof

2012-05-14

Objective: To investigate the anti-inflammatory effects of Sirt1 and its roles in steroidogenesis in Leydig cells.Design: In vitro cell culture study.Setting: Reproductive medical center.Animal(s): C57BL/6 male mice.Intervention(s): TM3 Leydig cells were treated with proinflammatory cytokines including tumor necrosis factor-α, interleukin-6, or interleukin-1β.Main Outcomes Measure(s): Sirt1 mRNA and protein levels were measured by real-time polymerase chain reaction and Western blotting in TM3 Leydig cells treated with proinflammatory cytokines. The cell viability was determined using MTT and BrdU incorporation assays. The effect of Sirt1 on the coactivation of steroidogenic factor 1 (SF-1) was characterized by coimmunoprecipitation and luciferase reporter assays.Result(s): Sirt1 mRNA and protein levels were significantly down-regulated by proinflammatory cytokines treatment in TM3 Leydig cells. Sirt1 agonist or overexpression could efficiently protect cytotoxicity induced by proinflammatory cytokines. Sirt1 promoted steroidogenesis through its coactivation of SF-1.Conclusion(s): Sirt1 plays protective roles and promotes steroidogenesis in Leydig cells through its anti-inflammatory actions and coactivation of SF-1.

Strain-specific spontaneous activation during mouse oocyte maturation - Corrected Proof

Yong Cheng, Zhisheng Zhong, Keith E. Latham — 2012-05-14

Objective: To examine whether spontaneous oocyte activation is determined by genetic differences and interacts with culture environment.Design: Experimental study.Setting: Temple University School of Medicine.Animal(s): C57BL/6, DBA/2, C3H/HeJ, and A/J strains, along with reciprocal F1 hybrid female mice (5–6 weeks).Intervention(s): Immature oocytes from different mouse strains collected and cultured in different maturation conditions, including different serum, serum replacement, bovine serum albumin (BSA), and follicle-stimulation hormone (FSH).Main Outcome Measure(s): The emission of first polar body, pronucleus formation, meiotic arrest, spontaneous activation, and expression of maturation regulators.Result(s): Oocytes from C57BL/6 mice display a high rate of delayed first meiotic division and spontaneous activation after the first meiotic division with in vitro maturation (IVM), and the second meiotic division with in vivo maturation (VVM) after superovulation. Spontaneous activation with IVM is sensitive to culture environment. Oocytes that spontaneously activated during the first meiotic division with IVM have unusual replicated sister chromatid pairs with slight connections at centromeres at first mitosis, whereas oocytes that activated in vivo display haploidization from the second meiotic division. Spontaneous activation is also seen in F1 hybrid oocytes, indicating a dominant trait from C57BL/6. Delayed meiosis was associated with reduced cyclin B and securin expression.Conclusion(s): Both mouse strain and culture environment have a statistically significant effect on the incidence of meiotic defects and spontaneous activation. Reduced expression of meiotic regulators may underlie this effect.

Studying nonobstructive azoospermia in cystinosis: histologic examination of testes and epididymis and sperm analysis in a Ctns−/− mouse model - Corrected Proof

2012-05-11

Objective: To study the pathogenesis of male infertility in cystinosis due to nonobstructive azoospermia, using a Ctns−/− mouse model.Design: Observational case-control study.Setting: Academic research laboratory.Animal(s): Male C57BL/6 Ctns−/− mice were compared with C57BL/6 wild-type (wt) mice.Intervention(s): None.Main Outcome Measure(s): Fertility was studied using litter size (n = 3 vs. n = 2). After animals were sacrificed, testes, epididymis, and vas deferens were removed for testicular cystine measurements (n = 5 vs. n = 6), histologic studies (n = 3 vs. n = 3), and sperm analysis (n = 3 vs. n = 3).Result(s): Mean testicular cystine content was significantly higher in Ctns−/− mice compared with wt mice (26.6 ± 1.22 vs. 0.1 ± 0.01 nmol cystine/mg protein). Testes of Ctns−/− mice had lower weight compared with wt mice (0.096 ± 0.009 g vs. 0.112 ± 0.004 g), but mice fertility was similar (litter size 6.6 ± 1.4 vs. 6.3 ± 2.6 pups). Neither histologic nor sperm abnormalities were found.Conclusion(s): The Ctns−/− mouse model generated on C57BL/6 background is not suitable for clarifying the pathogenesis of male infertility in cystinosis. The etiology of nonobstructive azoospermia in these patients remains unclear.

Human granulosa luteal cell oxidative phosphorylation function is not affected by age or ovarian response - Corrected Proof

2012-05-11

Objective: To safely prepare a functional autologous mitochondrial concentrate (MC) from follicular fluid (FF) cells, and to determine the effect of age and ovarian response on the oxidative phosphorylation (OXPHOS).Design: The nontoxicity of the MC was confirmed in human and mouse oocytes. The OXPHOS function was assessed by measuring the activity of succinate dehydrogenase (SDH) and cytochrome c oxidase (COX), and adenosine triphosphate (ATP) production in comparison with citrate synthase. The integrity of the mitochondrial DNA (mtDNA) was demonstrated by polymerase chain reaction (PCR).Setting: Tertiary hospital.Patient(s): A total of 40 patients undergoing IVF of heterogeneous ages and ovarian response.Animal(s): Superovulated 8- to 12-week-old female B6C3F1 mice.Intervention(s): None.Main Outcome Measure(s): A system for the preparation of functional nontoxic MC was established. The correlation between the mitochondrial mass and function to age and ovarian response was calculated. The integrity of mtDNA was demonstrated.Result(s): After injection into mouse oocytes, the MC did not interfere with parthenogenetic development. The MC OXPHOS function was intact. Total activity of SDH and COX was in correlation with the retrieved oocytes number, and in reverse correlation with age. However, after correction to the mitochondrial mass, COX and SDH activities were constant, unaffected by age or ovarian response. The mtDNA was intact in all samples, regardless of age and ovarian response.Conclusion(s): The function of the respiratory chain in mitochondria of FF cells is constant, unaffected by age or ovarian response.

Analysis of follicular fluid and serum markers of oxidative stress in women with infertility related to endometriosis - Corrected Proof

2012-05-11

Objective: To study the levels of four markers of oxidative stress in follicular fluid (FF) and plasma of patients with infertility related to endometriosis and controls.Design: Experimental study.Setting: University-affiliated hospital and infertility center.Patient(s): Ninety-one infertile women were included in the study (23 infertile women with endometriosis and 68 controls including infertile women due to tubal factor, male factor, or healthy egg donors).Intervention(s): Blood was obtained at the time of egg retrieval, and FF from the mature follicles of each ovary was centrifuged and frozen until analysis.Main Outcome Measure(s): Vitamin C and E, malondialdehyde, and superoxide dismutase concentrations in plasma and follicular fluid.Result(s): Women with endometriosis showed a lower vitamin C concentration in FF (12.7 ± 5.9 vs. 9.7 ± 6.9 μg/mL) and lower superoxide dismutase concentration in plasma (0.9 ± 1.4 vs. 0.5 ± 0.7 U/mL) compared with controls. Vitamin E plasma levels were significantly higher in women with endometriosis (8.1 ± 3.8 vs. 5.2 ± 3.2 μg/mL). A nonsignificant trend toward a lower plasma concentration of malondialdehyde was found in women with endometriosis.Conclusion(s): These findings suggest a lower antioxidant capacity in infertile women with endometriosis. Although a certain level of reactive oxygen species is required under physiological conditions, an altered balance between pro-oxidant and antioxidant activities may have an impact on folliculogenesis and adequate embryo development.

Effect of letrozole on estradiol production and P450 aromatase messenger RNA expression of cultured luteinized granulosa cells from women with and without endometriosis - Corrected Proof

Xiang Lu, Yu Wu, Xiao-Hong Gao, Yong-Wei Wang, Li Wang, Xiao-Xi Sun — 2012-05-11

Objective: To compare the estradiol production and P450 aromatase messenger RNA (mRNA) expression of cultured luteinized granulosa cells and the effect of letrozole on these parameters between women with and without endometriosis.Design: In vitro assays.Setting: Reproductive medical center.Patient(s): Patients undergoing in vitro fertilization (IVF): 23 patients with endometriosis and 19 controls without endometriosis.Intervention(s): Luteinized granulosa cells examined for estradiol levels and P450 aromatase mRNA expression in conditioned media at different letrozole concentrations of 0.0, 0.1, 1.0, and 10.0 μmol/L.Main Outcome Measure(s): Estradiol levels of the conditioned medium measured with an enzyme-linked immunosorbent assay (ELISA) kit and P450 aromatase mRNA expression determined by quantitative reverse transcription-polymerase chain reaction (QT RT-PCR).Result(s): The estradiol concentration of the conditioned media and P450 aromatase mRNA expression in the endometriosis group were statistically significantly lower than that of the control group, irrespective of letrozole concentrations. A statistically significant reduction of these two parameters was observed in both endometriosis and control groups at letrozole concentrations of 1 μmol/L and 10 μmol/L, but there were no statistically significant differences between letrozole concentrations of 1 μmol/L and 10 μmol/L. The number of high-quality embryos in the endometriosis group was statistically significantly lower than that of the control group.Conclusion(s): Lower estradiol production and P450 aromatase mRNA expression of cultured granulosa cells were found in women with endometriosis. Letrozole in the conditioned media further reduced these parameters.

Infertility, Diagnosis, Management, and IVF - Corrected Proof

John E. Buster — 2012-05-11

The title of this text is hardly imaginative. It does, however, describe exactly the content of this new text edited by Anil K. Dubey, Ph.D., a traditionally trained and scholarly basic scientist who is now IVF laboratory director at the George Washington University Reproductive Medicine Center. The text is a comprehensive assembly of contributions from 50 highly accomplished clinicians, basic scientists, administrators, and ethicists who have crafted their respective areas of expertise into 8 sections and 25 chapters. The work has a substantial international flavor, as its contributors comprise a diverse representation of European, Middle Eastern, Indian, and North American contributors.

Does ovulation induction with follicle-stimulating hormone still have a future in polycystic ovary syndrome? - Corrected Proof

Robert John Norman — 2012-05-09

Polycystic ovary syndrome (PCOS) is a common condition, regardless of the range of definitions available . Lack of regular ovulation is a cardinal component of the majority of presentations, with associated subfertility being a common reason for medical consultation. Initiation and successful conclusion of a pregnancy for women with PCOS in a timely, cost-effective, and safe manner is a skill required of all fertility specialists.

Epigenetics and vitrification of embryos: one step forward and many raised equivocal questions - Corrected Proof

Zeev Blumenfeld — 2012-05-07

In this issue of Fertility and Sterility, Zhao et al. have found that H19 putative imprinted control region (ICR) level of methylation significantly increased in vitrified two-cell bovine embryos and the generated blastocysts. They have also observed that incubation of vitrified-thawed 2-cell embryos with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-dC) significantly reduced H19 ICR methylation and increased H19 expression by reverse transcription–polymerase chain reaction in the blastocysts derived from the vitrified embryos compared with those in fresh embryos.

Peritoneal cytokines and adhesion formation in endometriosis: an inverse association with vascular endothelial growth factor concentration - Corrected Proof

2012-04-30

Objective: To evaluate inflammatory/angiogenic cytokines—interleukin-1β (IL-1β), IL-6, IL-8, IL-12, interferon-γ (IFN-γ), tumor necrosis factor (TNF), and vascular endothelial growth factor A (VEGF-A)—in the peritoneal fluid of patients with endometriosis in relation to the occurrence and severity of pelvic adhesions and in control women without pelvic pathology.Design: Case-control study.Setting: University research institution and hospital.Patient(s): Sixty-five women with laparoscopically and histopathologically confirmed endometriosis, including 40 women with pelvic adhesions, and 37 control women without pelvic pathology.Intervention(s): Peritoneal fluid aspirated during routine diagnostic laparoscopic examination.Main Outcome Measure(s): Cytokines evaluated in the peritoneal fluid via specific enzyme-linked immunosorbent assays.Result(s): Endometriosis and the revised American Fertility Society score of this disease were associated with statistically significantly increased levels of peritoneal IL-6 and IL-8 whereas the incidence and score of endometriosis-related pelvic adhesions were negatively associated with increased levels of VEGF-A. Notably, the concentration of VEGF-A predicted adhesion development and severity after adjustment for endometriosis severity. The adhesion score also correlated with increased levels of IL-6; however, after adjustment for endometriosis severity, the effect of this cytokine was no longer statistically significant.Conclusion(s): Increased levels of VEGF-A may be associated with a decreased rate of pelvic adhesion formation in the course of endometriosis.

Uterus transplantation: animal research and human possibilities - Corrected Proof

Mats Brännström, Cesar Diaz-Garcia, Ash Hanafy, Michael Olausson, Andreas Tzakis — 2012-04-30

Uterus transplantation research has been conducted toward its introduction in the human as a treatment of absolute uterine-factor infertility, which is considered to be the last frontier to conquer for infertility research. In this review we describe the patient populations that may benefit from uterus transplantation. The animal research on uterus transplantation conducted during the past two decades is summarized, and we describe our views regarding a future research-based human attempt.

Antimüllerian hormone levels are independently related to ovarian hyperandrogenism and polycystic ovaries - Corrected Proof

2012-04-27

Objective: To determine the relationship of antimüllerian hormone (AMH) levels to polycystic ovaries and ovarian androgenic function.Design: Prospective case-control study.Setting: General clinical research center.Participant(s): Eumenorrheic asymptomatic volunteers without (V-NO; n = 19; reference population) or with (V-PCO; n = 28) a polycystic ovary and hyperandrogenemic anovulatory subjects grouped according to ovarian function into typical PCOS (PCOS-T; n = 37) and atypical PCOS (PCOS-A; n = 18).Intervention(s): Pelvic ultrasonography, short dexamethasone androgen-suppression test (SDAST), and GnRH agonist (GnRHag) test.Main Outcome Measure(s): Baseline AMH levels were related to polycystic ovary status, testosterone response to SDAST, and 17-hydroxyprogesterone response to GnRHag test.Result(s): AMH levels correlated with SDAST and GnRHag test outcomes. AMH was elevated (>6.2 ng/mL) in 32% of V-PCO versus 5% V-NO. The 21% of V-PCO who met Rotterdam PCOS criteria all had functional ovarian hyperandrogenism, but AMH levels were similar to nonhyperandrogenic V-PCO. AMH >10.7 ng/mL discriminated V-PCO from PCOS with 96% specificity and 41% sensitivity for PCOS-T, and insignificantly for PCOS-A.Conclusion(s): AMH levels are independently related to ovarian androgenic function and polycystic ovaries. Very high AMH levels are specific but insensitive for PCOS. In the absence of hyperandrogenism, moderate AMH elevation in women with normal-variant polycystic ovaries seems to indicate an enlarged oocyte pool.

Erratum - Corrected Proof

2012-04-26

In the article, “Sperm DNA damage measured by the alkaline Comet assay as an independent predictor of male infertility and in vitro fertilization success” (Fertil Steril 2011:95;652–7), the data provided in Table 3 under the column “Male Infertility” were interim data using just 15 of the 20 donors rather than using the complete group of 20 donors and 75 infertile males. The corrected values including all 20 donors are as in the amended table below. The authors regret the error.

Screening for partial AZFa microdeletions in the Y chromosome of infertile men: is it of clinical relevance? - Corrected Proof

2012-04-26

Objective: To evaluate the frequency of complete and partial AZFa Y-chromosome microdeletions among infertile Israeli men. To review the published frequencies and histologic findings of AZFa deletions.Design: Retrospective study.Setting: Academic medical center.Patient(s): A total of 1,260 infertile Israeli men. Literature review (2000–2010) of reports on men with AZFa deletions and their testicular findings.Intervention(s): The DNA of 1,260 infertile men was evaluated for AZF microdeletions. The DNA of 657 of them with undetected microdeletions was analyzed for partial AZFa deletion in the USP9Y and DDX3Y genes using sequence-tagged sites beyond EAA/EMQN recommendations.Main Outcome Measure(s): The frequency of complete and partial AZFa microdeletions. Availability of sperm cells for intracytoplasmic sperm injection in men with complete/partial microdeletions.Result(s): Two men had complete AZFa deletion (a frequency of 0.28% among nonobstructive azoospermic men). None had partial AZFa deletions.Conclusion(s): The likelihood of finding sperm cells in men with complete AZFa deletions is negligible. Complete AZFa deletion is rare and usually associated with azoospermia and absence of sperm cells in testicular tissue. The low frequency of partial AZFa deletions and the inconsistent prospects for spermatogenesis reported in the literature question the need for routine assessment of microdeletions in genes, such as USP9Y or DDX3Y.

Position on donors and smallpox vaccine: a committee opinion - Corrected Proof

2012-04-26

Although there is presently no definitive evidence linking vaccinia virus transmission through reproductive cells, SART/ASRM accordingly recommends that ART practitioners consider deferring donors who have recently received smallpox vaccine or contracted symptomatic vaccinia virus infection through close contact with a vaccine recipient (until after the vaccine or infectious scab has spontaneously separated). Good donor practice further suggests that donors who are not in good health, including those with recent complications from smallpox vaccine, should be similarly deferred. (This document was reviewed by the ASRM Practice Committee in 2011).

Recommendations for development of an emergency plan for in vitro fertilization programs: a committee opinion - Corrected Proof

2012-04-26

All in vitro fertilization (IVF) programs and clinics should have a plan to protect fresh and cryopreserved human tissue (embryos, oocytes, sperm) and to provide for continuation of patient care in the event of an emergency or natural disaster. This document was reviewed and affirmed by the Practice Committee in 2011.Earn online CME credit related to this document at www.asrm.org/elearn

Fertility treatment when the prognosis is very poor or futile: a committee opinion - Corrected Proof

The Ethics Committee of the American Society for Reproductive Medicine — 2012-04-26

The Ethics Committee recommends development of evidence-based policies that are patient-centered for each in vitro fertilization (IVF) center. In most cases, the provision of futile therapies is not ethically justiﬁable. For those treatments with very poor success rates, clinicians must be vigilant in their presentation of risks, beneﬁts, and alternatives. This document was reviewed in January 2012. This version replaces the previous version of this document, published in 2009.Earn online CME credit related to this document at www.asrm.org/elearn

Adverse perinatal outcome and in vitro fertilization singleton pregnancies: what lies beneath? Further evidence to support an underlying role of the modifiable hormonal milieu in in vitro fertilization stimulation - Corrected Proof

Suleena Kansal Kalra — 2012-04-26

The findings reported by Imudia et al. contribute to the emerging body of literature identifying modifiable aspects of IVF treatment that are associated with risk in singleton births. The most novel aspect of this study is that it presents a “threshold” effect of supraphysiologic E2 levels and subsequent antenatal and perinatal adverse outcome. In this study, outcomes were assessed in a group of patients undergoing IVF treatment and exposed to an elevated peak E2 level at a single institution, defined as an E2 level exceeding the 90th percentile on the day of hCG administration (>3,950 pg/mL), and compared to a group of patients undergoing IVF treatment with levels of E2 below that cutoff. Specifically, the study reports that the odds of preeclampsia was fourfold greater and small for gestational age infants was ninefold greater in patients undergoing IVF treatment with an elevated peak E2 level compared to women with a lower peak E2 level. No difference in preterm delivery was found.

Erratum - Corrected Proof

2012-04-26

In the article, “Is there a place for corifollitropin alfa in IVF/ICSI cycles? A systematic review and meta-analysis,” (Fertil Steril 2012;97:876–85), regarding OHSS incidence per woman randomized in four papers reviewed, the number needed to harm (NNT) was reported as 1, with an absolute risk increase of 1% after corifollitropin alfa. The correct NNT is 100. The authors regret the error.

Morphometric-stereological and functional epididymal alterations and a decrease in fertility in rats treated with finasteride and after a 30-day post-treatment recovery period - Corrected Proof

2012-04-23

Objective: To evaluate morphometric-stereological changes in the epididymal caput, sperm quality, and fertility parameters in rats treated with finasteride and after a 30-day post-treatment recovery period.Design: Experimental study in a research laboratory.Setting: Reproductive biology research laboratory.Animal(s): Male and female Sprague Dawley rats.Intervention(s): Treatment with finasteride (5 mg/kg/day) for 56 days followed by 30 days without treatment.Main Outcome Measure(s): Serum hormone analyses, morphometric-stereological and ultrastructural evaluation of the epididymal caput, sperm transit time, natural mating, in utero insemination, sperm membrane integrity, and fertility parameters.Result(s): Serum dihydrotestosterone levels in the finasteride group decreased by ∼40% compared with that of control rats. Ultrastructural analysis revealed significant reductions in several morphometric-stereological parameters of the epididymal caput. All parameters recovered significantly in the post-treatment period. There was no alteration in daily sperm production in the finasteride group. However, significant reductions in sperm transit time, motility, sperm membrane integrity, and fertility parameters were observed in rats treated with finasteride.Conclusion(s): Treatment with finasteride caused morphometric-stereological and functional changes in the epididymis and in sperm function that led to a reduction in fertility parameters. A 30-day post-treatment recovery period was insufficient to restore normal sperm motility, sperm transit time, and some fertility parameters.

Effect of laparoscopic excision of endometriomas on ovarian reserve: serial changes in the serum antimüllerian hormone levels - Corrected Proof

2012-04-23

Objective: To investigate the effect of laparoscopic endometrioma stripping on serum antimüllerian hormone (AMH) and the correlation between the clinicopathologic factors.Design: Prospective study.Setting: University hospital.Patient(s): Sixty-five women with endometriomas.Intervention(s): All patients underwent laparoscopic cystectomy. Serum AMH, FSH, LH, E2, and antral follicle count (AFC) were measured preoperatively, at 6 weeks, and at 6 months postoperatively. Specimens were analyzed histopathologically.Main Outcome Measure(s): The primary end point was to assess the ovarian reserve damage based on alterations of AMH and the secondary end point was to detect the changes in FSH, LH, E2, and AFC.Result(s): Serum AMH decreased significantly at the sixth month (61%) postoperatively. The FSH level increased significantly at the sixth week, but returned to normal at the sixth month. The AFC increased significantly at the sixth week and at the sixth month. The AMH level decrease was more evident in patients with the cyst <5 cm (65.7% vs. 41.3%). The AMH decrease was more in bilateral compared with unilateral endometriomas (67% versus 57%, respectively). No correlation was detected between the histopathologic analyses and tAMH level. Initially the AMH level was the only independent factor affecting the AMH decrease (odds ratio, 3.68; 95% confidence interval 1.66–8.14).Conclusion(s): Laparoscopic cystectomy of ovarian endometriomas causes a significant and progressive decline in serum AMH levels.

Activated glucocorticoid and eicosanoid pathways in endometriosis - Corrected Proof

2012-04-23

Objective: To define altered gene expression networks in endometriosis.Design: Experiments using endometriotic tissues and primary cells.Setting: Division of Reproductive Biology Research, Northwestern University.Patient(s): Premenopausal women.Intervention(s): Matched samples of eutopic endometrium and ovarian endometriosis (n = 8 patients) were analyzed by microarray and verified in a separate set of tissues (n = 6 patients). Experiments to define signaling pathways were performed in primary endometriotic stromal cells (n = 12 patients).Main Outcomes Measure(s): Using a genome-wide in vivo approach, we identified 1,366 differentially expressed genes and a new gene network favoring increased glucocorticoid levels and action in endometriosis.Result(s): Transcript and protein levels of 11β-hydroxysteroid dehydrogenase (HSD11B1), which produces cortisol, the biologically active glucocorticoid, were strikingly higher, whereas messenger RNA (mRNA) levels of the cortisol-degrading HSD11B2 enzyme were significantly lower in endometriotic tissue. Glucocorticoid receptor mRNA and protein levels were significantly higher in endometriosis. The inflammatory cytokine tumor necrosis factor robustly induced mRNA and protein levels of HSD11B1 and glucocorticoid receptor but suppressed HSD11B2 mRNA in primary endometriotic stromal cells, suggesting that tumor necrosis factor stimulates cortisol production and action. We also uncovered a subset of genes critical for prostaglandin synthesis and degradation, which favor high eicosanoid levels and activity in endometriosis.Conclusion(s): The proinflammatory milieu of the endometriotic lesion stimulates cortisol synthesis and action in endometriotic lesions.

Chromosomal abnormalities in embryos from couples with a previous aneuploid miscarriage - Corrected Proof

2012-04-23

Objective: To compare the incidence of chromosomal abnormalities in preimplantation embryos from couples undergoing preimplantation genetic screening (PGS) after previous aneuploid miscarriage after either natural conception (NC) or assisted reproductive technology (ART) versus fertile couples who underwent PGS for sex-linked diseases as a control group.Design: Retrospective study.Setting: IVF clinic.Patient(s): Patients with previous aneuploid conception undergoing PGS.Intervention(s): Embryo biopsy, fluorescence in situ hybridization.Main Outcome Measure(s): Embryo aneuploidy rates and pregnancy and implantation rates in couples with a previous aneuploidy for autosomes or sex chromosomes.Result(s): The overall rates of chromosomal abnormalities in groups with previous autosomal aneuploidy were significantly higher compared with the control group (67.8% for those whose previous aneuploidy arose after NC and 65.8% for those previously arising after ART, vs. 34.0%). No significant differences were observed in those with previous sex chromosome abnormalities compared with control subjects. Within couples with previous aneuploidies after NC, no difference existed in the incidence of chromosomal abnormalities compared with the ART groups. Clinical outcomes were better (trend) in patients with previous autosomal aneuploidy after NC.Conclusion(s): In preimplantation embryos, the incidence of chromosomal abnormalities due to a previous aneuploid miscarriage after either NC or ART is significantly higher than in the control group. Furthermore, this incidence is higher when the previous aneuploidy was for autosomes; PGS is recommended in these couples.

The association between fertility clinic performance and cycle volume: implications for public reporting of provider performance data - Corrected Proof

Dan Gong, Emre Seli — 2012-04-23

Objective: To quantitatively determine the relationship between fertility clinic performance and cycle volume, and to assess the implications for public reporting of provider performance data.Design: Retrospective longitudinal analysis.Setting: Clinic.Patient(s): The study population included 307 U.S. assisted reproductive technology (ART) clinics that continuously reported performance data to the Centers for Disease Control from 2003 to 2008.Intervention(s): None.Main Outcome Measure(s): Regression coefficients between pregnancy rate per cycle, live birth rate per cycle, or live birth rate per transfer and number of ART cycles performed.Result(s): Overall, there was no association found between a clinic's most recently reported success rate and its cycle volume. This finding was consistent across three time periods studied. Moreover, stratification analyses of clinics with greater than ±5%, ±10%, and ±20% change in success rates also found no association between clinic performance and cycle volume.Conclusion(s): As proxied by cycle volume data, patients seeking ART treatment do not seem to be influenced by positive or negative changes in a clinic's performance despite the public availability of this data. These results suggest that current public quality reporting encompassing success rates alone will not change patient behavior and therefore is insufficient to place salient competitive pressure on health care providers. Further research is necessary to define provider performance comprehensively and to determine the metrics, if any, to which patients respond.

Role of routine monitoring of liver and renal function during treatment of ectopic pregnancies with single-dose methotrexate protocol - Corrected Proof

2012-04-23

Objective: To assess whether or not baseline serum transaminases and creatinine measurements, before administration of methotrexate, identified significant liver or kidney disease, which have the potential to alter the management plan for the treatment of ectopic pregnancies.Design: This is a retrospective study of patients treated for ectopic pregnancy.Setting: Women's emergency room and reproductive endocrinology office at a teaching hospital over a 3-year period.Patient(s): Women presenting for treatment of ectopic pregnancy.Intervention(s): None.Main Outcome Measure(s): Assessment of baseline serum transaminases and creatinine measurements before administration of methotrexate to identify significant liver or kidney disease.Result(s): A total of 383 patients were managed for ectopic pregnancy from January 2006 to December 2008. Of these, 320 patients received methotrexate as part of their treatment. No patient was denied treatment with methotrexate secondary to concerns regarding liver or renal function. No complication related to methotrexate administration was documented. A subgroup of 81 patients had pre- and postadministration labs, and no significant difference was noted upon comparing the values.Conclusion(s): Routine measurement of serum aspartate aminotransferase and creatinine levels may not be necessary before instituting a single-dose methotrexate treatment regimen for the management of ectopic pregnancy.

Running interference - Corrected Proof

Nanette Santoro — 2012-04-23

Carpenter et al. report on secondary data from the MsFlash randomized, controlled trial of escitalopram for hot flashes in menopausal women. The trial demonstrated a statistically significant reduction in hot flash frequency versus placebo at 8 weeks in the primary trial . Hot flash severity decreased in a similar direction and magnitude to frequency. The study demonstrated a marked placebo effect, with a decrease in hot flash frequency of 3 per day by 8 weeks in the women taking placebo. The treatment effect was slightly more, 4.6 hot flashes per day.

Spontaneous pregnancies among couples previously treated by in vitro fertilization - Corrected Proof

2012-04-23

Objective: To determine the frequency of live births following spontaneous pregnancy (BSP) and to examine their associated factors among couples who have unsuccessfully or successfully experienced fertility treatments.Design: Retrospective cohort.Setting: Eight IVF centers.Patient(s): A total of 2,134 couples who began IVF treatment in the centers in 2000–2002 and were followed up by a postal questionnaire sent 7–9 years after they started treatment in the inclusion center.Intervention(s): None.Main Outcome Measure(s): Rates of BSP and factors associated with BSP. Univariate and multivariate analyses were conducted using logistic regression.Result(s): The BSP rate was 17% (218/1,320) among couples who had previously had a child through medical treatment and 24% (193/814) among couples who had remained childless after treatment. In both groups, the probability of BSP was higher among younger women and increased with a smaller number of IVF attempts. Probability was also higher when the cause of infertility was unexplained.Conclusion(s): Our results should give hope to couples who have been unsuccessfully treated by IVF, especially young couples with unexplained infertility. Nonetheless, it should be remembered that the BSP rates are cumulative rates observed over a long period of time and that these couples have a very low monthly probability of conceiving.

The role of the peritoneal cavity in adhesion formation - Corrected Proof

Philippe R. Koninckx, Anastasia Ussia, Leila Adamyan — 2012-04-23

The article by Barcz et al. deserves a comment since it should make us think. Differences in peritoneal fluid constituents between women with and without endometriosis have been studied repetitively since the late 1970s in order to gain insight into the pathophysiology of endometriosis and associated infertility. Endometriosis is associated with a low-grade inflammation with more and more activated macrophages in peritoneal fluid. Despite the huge amount of data available, as this article also contributes to the data of cytokine concentrations, a comprehensive conclusion was never reached. More specifically, for most factors it remains speculative which are contributing to the development of endometriosis and which are a consequence of endometriosis .

Nonsurgical dilation for vaginal agenesis is promising, but better research is needed - Corrected Proof

2012-04-20

We write with concerns about the article “Mayer-Rokitansky-Küster-Hauser syndrome: a review of 245 consecutive cases managed by a multidisciplinary approach with vaginal dilators” . Although we agree with the investigators that nonsurgical dilation supported by a multidisciplinary team is a promising approach, we also wish to highlight the deficiencies in this report.

Hairless or fertile? Finasteride leads to epididymal changes and infertility in rats - Corrected Proof

Keith Jarvi — 2012-04-20

As most of the readers are aware, 5 α-reductase converts testosterone to the more potent androgen, dihydrotestosterone (DHT). Male alopecia, or hair loss, in many situations is related to elevated androgen levels at the hair follicle (so called androgenic alopecia). Garcia et al. point out that androgenic alopecia is an incredibly common condition affecting close to one third of men over 30 years of age with many men using finasteride to present hair loss.

Successful pregnancy in vitrified/warmed blastocyst intrafallopian transfer - Corrected Proof

Gernot Tews, Omar Shebl, Marianne Moser, Thomas Ebner — 2012-04-19

Objective: To analyze whether the use of blastocyst intrafallopian transfer is a feasible option in a case of repeated difficult ET.Design: Case report.Setting: Public hospital.Patient(s): Forty-year old nulliparous patient.Intervention(s): Transfer of two vitrified/warmed blastocysts into the right tube by means of laparoscopy.Main Outcome Measure(s): Successful ET, clinical pregnancy.Result(s): Successful ET procedure resulting in positive ß-hCG and clinical pregnancy.Conclusion(s): In cases of repeated difficult ETs (regardless of whether the patient shows cervical adhesions or any type of genital malformations), blastocyst intrafallopian transfer can be a successful alternative approach.

Is chromosome testing of the second miscarriage cost saving?: A decision analysis of selective versus universal recurrent pregnancy loss evaluation - Corrected Proof

Lia A. Bernardi, Beth A. Plunkett, Mary D. Stephenson — 2012-04-19

Objective: To compare the cost of selective recurrent pregnancy loss (RPL) evaluation, which is defined as RPL evaluation if the second miscarriage is euploid, versus universal RPL evaluation, which is defined as RPL evaluation after the second miscarriage. Traditionally, an RPL evaluation is instituted after the third miscarriage. However, recent studies suggest evaluation after the second miscarriage, which dramatically increases health care costs. Alternatively, chromosome testing of the second miscarriage, to determine whether an RPL evaluation is required, has been proposed.Design: Decision-analytic model.Setting: Academic medical center.Patient(s): Couples experiencing a second miscarriage of less than 10 weeks size.Intervention(s): Selective versus universal RPL evaluation after the second miscarriage.Main Outcome Measure(s): Estimated cost for selective versus universal RPL evaluation.Result(s): The estimated cost of selective RPL evaluation after the second miscarriage was $3,352, versus $4,507 for universal RPL evaluation, resulting in a cost savings of $1,155. With stratification by maternal age groups, selective RPL evaluation resulted in increased cost savings with advancing maternal age groups.Conclusion(s): Selective RPL evaluation, which is based upon chromosome testing of the second miscarriage, is a cost-saving strategy for couples with RPL when compared with universal RPL evaluation. With advancing maternal age groups, the cost savings increased.

The risk of gestational diabetes mellitus among Mexican women with a history of infertility and polycystic ovary syndrome - Corrected Proof

2012-04-16

Objective: To study the incidence of gestational diabetes mellitus (GDM) in Mexican women with a history of infertility and polycystic ovary syndrome (PCOS) compared with women without PCOS matched by age, pregestational body mass index (BMI), and parity.Design: Historic cohort study.Setting: Level three medical institution.Patient(s): Group 1 (n = 52), women with a history of infertility and PCOS, and group 2 (n = 52), women without PCOS. Inclusion criteria were singleton pregnancy with ≤13 weeks of gestation. Exclusion criteria were pregestational diabetes mellitus and/or concomitant diseases.Intervention(s): Diagnosis of GDM was based on a 3-hour, 100-g oral glucose tolerance test (GTT) performed during the second trimester.Main Outcome Measure(s): Incidence and relative risk (RR) for GDM.Result(s): The incidence of GDM was 26.9% and 9.6% for groups 1 and 2, respectively (RR = 2.8; 95% confidence interval 1.08–7.2). No other between-group differences were observed in the incidence of miscarriage, preterm birth, premature rupture of membranes, preeclampsia, stillbirth, fetal malformations, or small or large for gestational age newborns.Conclusion(s): Pregnant Mexican women with a history of infertility and PCOS are at increased risk for developing GDM. This risk should be considered beginning early in the second trimester for a timely intervention and to improve the maternal–fetal prognosis.

Recommendations for practices utilizing gestational carriers: an ASRM Practice Committee guideline - Corrected Proof

2012-04-13

This document provides the latest recommendations for evaluation of gestational carriers and intended parents. It incorporates recent information from the US Centers for Disease Control and Prevention, the US Food and Drug Administration, and the American Association of Tissue Banks, with which all programs offering gestational carrier services must be thoroughly familiar.Earn CME credit for this document at www.asrm.org/eLearn

Influence of embryo transfer on embryo preimplantation development - Corrected Proof

2012-04-13

Objective: To investigate the impact of injection speeds of the transferred load on embryo development.Design: A laboratory model for in vitro simulation of ET was developed to investigate the impact of varying injection speeds of the transferred load on embryo development.Setting: Academic research institutes of reproduction biotechnology and private centers of reproductive medicine.Animal(s): Mouse hybrid F1 females (C57bl/10J × CBA-H; N = 15) aged 2–3 months.Intervention(s): In vitro exposure of mouse embryos with either the fast ET (ejection speed, >1 m/s) or slow ET (ejection speed, <0.1 m/s) and consecutive culture for 36 hours.Main Outcome Measure(s): Development rate, morphology and apoptotic index of embryos.Result(s): The development rate was the slowest in embryos exposed to the fast ET. Morphological changes in response to ET were observed only among embryos exposed to the fast ET. The mean apoptotic index was 17.6% in the group exposed to the fast ET, 5.6% in the group exposed to the slow ET, and 2.58% in the control group.Conclusion(s): A reduction of the ejection speed of the transferred load allows avoidance of a developmental delay and diminishes injury of the embryos. Therefore, it is reasonable to suggest transferring the embryos at the lowest possible ejection speed.

Etiology of ovarian hyperstimulation syndrome - Corrected Proof

Raoul Orvieto — 2012-04-13

I read with interest the recently published discussion on the etiology and prevention of ovarian hyperstimulation syndrome (OHSS) . Although the review comprehensively covered its aims, there are some issues that should be highlighted.

Elimination of ovarian hyperstimulation syndrome - Corrected Proof

Raoul Orvieto — 2012-04-13

I read with interest the recently published discussion on the etiology and prevention of ovarian hyperstimulation syndrome (OHSS) . Although the reviews comprehensively covered their aims, there are some issues that should be highlighted.

Reply of the Authors - Corrected Proof

David R. Meldrum — 2012-04-13

I appreciate the letter by Dr. Orvieto, which allows reemphasis of some of the points we made, and, more important, raises two preventive strategies that were not included in any of our reviews.

Reply of the Authors - Corrected Proof

Sérgio Reis Soares — 2012-04-13

We thank Dr. Orvieto for the interest in our recent publication on the etiology of ovarian hyperstimulation syndrome (OHSS) and the use of dopamine agonists . In his letter, Dr. Orvieto expresses his belief in the absence of significant evidence to ascribe to vascular endothelial growth factor (VEGF) a key role in the genesis of the syndrome. To support this view, a 1997 study is quoted in which women of advanced reproductive age and not at risk for OHSS had higher follicular fluid (FF) concentrations of VEGF than younger women . We do not see any conflict between such a finding and the actual role of VEGF in the etiology of OHSS. Increased vascular permeability (VP) leading to OHSS is the consequence of global VEGF activity that is, by its turn, related to a high number of follicles and active granulosa (GC)/luteal cells, rather than to VEGF concentration in individual follicles of women with a low ovarian response.

Reply of the Authors - Corrected Proof

Mohamed Aboulghar — 2012-04-13

I read with interest the letter by Dr. Orvieto commenting on the article “Agonist and antagonist coast” . We agree that a high E2 level is not always associated with severe ovarian hyperstimulation syndrome (OHSS); however, a high E2 level has an important role in the prediction of OHSS and lowering the E2 level helped to prevent OHSS . It was hypothesized that coasting diminishes the functional granulosa cell (GC) cohort, which may possibly result in the reduction of the chemicals that augment fluid extravascular accumulation .

Recording and sorting live human sperm undergoing acrosome reaction - Corrected Proof

2012-04-11

Objective: To develop and evaluate a method to detect acrosome reaction (AR) in live human sperm.Design: Prospective study.Setting: Basic research laboratory.Patient(s): Human semen samples with normal parameters obtained from healthy donors.Intervention(s): Acrosome reaction assays.Main Outome Measure(s): Fluorescence assessment of AR.Result(s): Evaluating acrosomal exocytosis in live human sperm is challenging. In this study, we report that in reacting sperm, Pisum sativum agglutinin conjugated to fluorescein isothiocyanate rapidly permeates into the acrosome when fusion pores open and stabilizes the acrosomal matrix, preventing the dispersal of the granule contents.Conclusion(s): Fluorescent Pisum sativum agglutinin can be used to visualize AR in real time, to determine the percentage of sperm undergoing exocytosis upon stimulation, and to separate the population of reacting sperm by flow cytometry.

Serum progesterone level effects on the outcome of in vitro fertilization in patients with different ovarian response: an analysis of more than 10,000 cycles - Corrected Proof

Bei Xu, Zhou Li, Hanwang Zhang, Lei Jin, Yufeng Li, Jihui Ai, Guijin Zhu — 2012-04-11

Objective: To investigate the relationship between serum P levels on the day of hCG administration and pregnancy outcomes in different responders undergoing IVF.Design: Retrospective study.Setting: Teaching hospital.Patient(s): A total of 11,055 women who underwent their first IVF/intracytoplasmic sperm injection cycles and a subgroup of 4,021 women undergoing frozen-embryo transfer (FET) cycles.Intervention(s): Patients underwent IVF-ET with the long GnRH agonist protocol. The ovarian response was classified as high (≥20 oocytes; n = 2,023), poor (≤4 oocytes; n = 827), or intermediate (remaining cases; n = 8,205) according to the number of oocytes retrieved. Clinical outcomes of IVF-ET and FET cycles were analyzed according to plasma P levels.Main Outcome Measure(s): Ongoing pregnancy rates (PRs).Result(s): Ongoing PRs in fresh cycle were inversely associated with serum P levels on the day of hCG administration for all patients. Different P threshold concentrations were determined according to different ovarian response: We proposed a serum P level of 1.5 ng/mL as the threshold for poor responders, 1.75 ng/mL for intermediate responders, and 2.25 ng/mL for high responders. Our study does not show negative results for elevated P levels on oocyte performance in terms of fertilization, cleavage rate, or PR of FET cycles within different ovarian responses, offering no evidence for a detrimental effect of high P on oocyte quality.Conclusion(s): Elevated P levels on the day of hCG administration negatively influence PR regardless of different ovarian responses, although increased P threshold concentration is associated with better ovarian responses. The detrimental effect of P elevation on PR seems to be unrelated to oocyte quality in all responders.

Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization - Corrected Proof

2012-04-11

Objective: To assess the impact of elevated peak serum E2 levels (EPE2; defined as levels >90th percentile) on the day of hCG administration during controlled ovarian hyperstimulation (COH) for IVF on the likelihood for small for gestational age (SGA), preeclampsia (PreE), and preterm delivery (PTD) in singleton pregnancies.Design: Retrospective cohort study.Setting: Tertiary-care academic medical center.Patient(s): Singleton live-birth pregnancies conceived after fresh IVF-ET.Intervention(s): None.Main Outcome Measure(s): The delivery rate of SGA infants and the development of PreE and PTD in patients with and without EPE2.Result(s): Patients with EPE2 during COH were more likely to deliver SGA infants (7 [26.9%] vs. 10 [3.8%]; odds ratio [OR], 95% confidence interval [CI] {9.40, 3.22–27.46}) and develop PreE (5 [18.5%] vs. 12 [4.5%]; adjusted OR, 95% CI {4.79, 1.55–14.84}). No association was found between EPE2 and the likelihood for delivery before 37 weeks, 35 weeks, or 32 weeks of gestation. Receiver operating characteristic analysis revealed that EPE2 level predicted adverse obstetrical outcome (SGA + PreE) with 38.5% and 91.7% sensitivity and specificity, respectively. Using a serum peak E2 cutoff value of 3,450 pg/mL (>90th percentile level), the positive predictive value was 37%, while the negative predictive value was 92%.Conclusion(s): EPE2 level (>3,450 pg/mL) on the day of hCG administration during COH is associated with greater odds of developing PreE and delivery of an SGA infant in singleton pregnancies resulting from IVF cycles.

Circulating vitamin D correlates with serum antimüllerian hormone levels in late-reproductive-aged women: Women's Interagency HIV Study - Corrected Proof

2012-04-11

Objective: To study the correlation between circulating 25-hydroxyvitamin D (25OH-D) levels and serum antimüllerian hormone (AMH) in women enrolled in the Women's Interagency HIV Study.Design: Cross-sectional study.Setting: None.Patient(s): All premenopausal women (n = 388) with regular menstrual cycles were included and subdivided into three groups: group 1 with age <35 years (n = 128), group 2 with age 35–39 years (n = 119), and group 3 with age ≥40 years (n = 141).Intervention(s): Serum for 25OH-D, AMH, fasting glucose and insulin, and creatinine levels.Main Outcome Measure(s): Correlation between 25OH-D and AMH before and after adjusting for HIV status, body mass index, race, smoking, illicit drug use, glucose and insulin levels, estimated glomerular filtration rate, and geographic site of participation.Result(s): After adjusting for all covariates, the regression slope in all participants for total 25OH-D predicting log10AMH for 25-year-olds (youngest participant) was −0.001 (SE = 0.008); and for 45-year-olds (oldest participant) the corresponding slope was +0.011 (SE = 0.005). Fasting insulin level was negatively correlated with serum AMH. The regression slope for the correlation between 25OH-D and AMH in group 1 was +0.002 (SE = 0.006); in group 2 was +0.006 (SE = 0.005); and in group 3 was +0.011 (SE = 0.005). There was no association between HIV and AMH.Conclusion(s): A novel relationship is reported between circulating 25OH-D and AMH in women aged ≥40 years, suggesting that 25OH-D deficiency might be associated with lower ovarian reserve in late-reproductive-aged women.