Cryopreservation of human spermatozoa with minimal non-permeable cryoprotectant.

Cryopreservation of human spermatozoa is a commonly used technique in assisted reproduction, however freezing low concentrations of sperm while maintaining adequate post-thaw motility remains a challenge. In an effort to optimize post-thaw motility yields, low volumes of human sperm were frozen in polyimide-coated fused silica micro-capillaries using 0.065 M, 0.125 M, 0.25 M, or 0.5 M trehalose as the only cryoprotectant. Micro-capillaries were either initially incubated in liquid nitrogen vapor before plunging into liquid nitrogen, or directly plunged into liquid nitrogen. Post thaw sperm counts and motility were estimated. Spermatozoa that were initially incubated in liquid nitrogen vapor had greater post thaw motility than those plunged immediately into liquid nitrogen independent of trehalose concentration. The protective effect of 0.125 M d-glucose, 3-O-methyl-d-glucopyranose, trehalose, sucrose, raffinose, or stachyose were evaluated individually. Trehalose and sucrose were the most effective cryoprotectants, recovering 69.0% and 68.9% of initial sperm motility, respectively.

Ovarian stimulation and in-vitro fertilization outcomes of cancer patients undergoing fertility preservation compared to age matched controls: a 17-year experience.

PURPOSE: To compare the in-vitro fertilization (IVF) outcomes of cancer patients who underwent oocyte retrieval and embryo/oocyte cryopreservation prior to gonadotoxic therapy to those of age and time-matched controls with tubal factor infertility. METHODS: All cancer patients who underwent embryo/oocyte cryopreservation at our institution from 1997 to 2014 were reviewed. Primary outcomes were total dose of gonadotropins used, number of oocytes retrieved, and number of 2pn embryos obtained. Outcomes were compared to age-matched controls with tubal-factor infertility who underwent a fresh embryo transfer within the same relative time period as the IVF cycle of the cancer patient. RESULTS: Sixty-three cancer patients underwent 65 IVF cycles, and 21 returned for frozen embryo transfer. One hundred twenty-two age-matched controls underwent IVF cycles with fresh transfer, and 23 returned for frozen embryo transfer. No difference was seen between cancer patients and controls with respect to total ampules of gonadotropin used (38.0 vs. 35.6 respectively; p = 0.28), number of oocytes retrieved (12.4 vs. 10.9 respectively; p = 0.36) and number of 2pn embryos obtained (6.6 vs. 7.1 respectively; p = 0.11). Cumulative pregnancy rate per transfer for cancer patients compared to controls was 37 vs. 43 % respectively (p = 0.49) and cumulative live birth rate per transfer was 30 vs. 32 % respectively (p = 0.85). Cancer patients had a higher likelihood of live birth resulting in twins (44 vs. 14 %; p = 0.035). CONCLUSIONS: Most IVF outcomes appear comparable for cancer patients and age-matched controls. Higher twin pregnancy rates in cancer patients may reflect lack of underlying infertility or need for cancer-specific transfer guidelines.

Processed meat intake is unfavorably and fish intake favorably associated with semen quality indicators among men attending a fertility clinic.

Emerging literature suggests that men's diets may affect spermatogenesis as reflected in semen quality indicators, but literature on the relation between meat intake and semen quality is limited. Our objective was to prospectively examine the relation between meat intake and indicators of semen quality. Men in subfertile couples presenting for evaluation at the Massachusetts General Hospital Fertility Center were invited to participate in an ongoing study of environmental factors and fertility. A total of 155 men completed a validated food-frequency questionnaire and subsequently provided 338 semen samples over an 18-mo period from 2007-2012. We used linear mixed regression models to examine the relation between meat intake and semen quality indicators (total sperm count, sperm concentration, progressive motility, morphology, and semen volume) while adjusting for potential confounders and accounting for within-person variability across repeat semen samples. Among the 155 men (median age: 36.1 y; 83% white, non-Hispanic), processed meat intake was inversely related to sperm morphology. Men in the highest quartile of processed meat intake had, on average, 1.7 percentage units (95% CI: -3.3, -0.04) fewer morphologically normal sperm than men in the lowest quartile of intake (P-trend = 0.02). Fish intake was related to higher sperm count and percentage of morphologically normal sperm. The adjusted mean total sperm count increased from 102 million (95% CI: 80, 131) in the lowest quartile to 168 million (95% CI: 136, 207) sperm in the highest quartile of fish intake (P-trend = 0.005). Similarly, the adjusted mean percentages of morphologically normal sperm for men in increasing quartiles of fish intake were 5.9 (95% CI: 5.0, 6.8), 5.3 (95% CI: 4.4, 6.3), 6.3 (95% CI: 5.2, 7.4), and 7.5 (95% CI: 6.5, 8.5) (P-trend = 0.01). Consuming fish may have a positive impact on sperm counts and morphology, particularly when consumed instead of processed red meats.

The impact of supraphysiologic serum estradiol levels on peri-implantation embryo development and early pregnancy outcome following in vitro fertilization cycles.

PURPOSE: To determine the impact of elevated serum estradiol levels (EE2-defined as levels > 90th percentile) on the day of hCG administration during IVF on oocyte fertilization, embryo development, implantation, clinical pregnancy and miscarriage rates. METHODS: A total of 2,995 consecutive IVF cycles in 1,889 patients with non-donor oocyte retrieval resulting in fresh embryo transfer between 1/1/2005 and 12/31/2011 were analyzed. Cycles were stratified by serum E2 level on the day of hCG administration into those with levels >90th percentile and ≤ 90th percentile. Rates of normal fertilization, embryo development, positive pregnancy test, implantation, clinical pregnancy and spontaneous miscarriage were compared. RESULTS: Serum estradiol above the 90th percentile on the day of hCG administration was associated with a significantly lower rate of normal fertilization (68.6 ± 20 vs. 71.6 ± 21, p = 0.02) when compared with patients with a lower serum estradiol threshold. The proportion of embryos that progressed from 2PN to 6-8 cell on day 3 was not different between the two groups. Although rates of positive pregnancy test (55.2 % vs. 57 %), implantation (26.4 % vs. 28.5 %) and clinical pregnancy (45.5 % vs. 49.4 %) were lower in patients with a higher estradiol threshold, these differences were not statistically significant. Similarly, there was no difference in the spontaneous miscarriage rates between the two groups (8.4 % vs. 7.1 %). CONCLUSIONS: Serum estradiol levels above the 90th percentile on the day of hCG administration is associated with lower oocyte fertilization rate; however, such levels do not impact embryo development, implantation, clinical pregnancy or spontaneous miscarriage rates.

Frozen-thawed embryo transfer cycles: clinical outcomes of single and double blastocyst transfers.

PURPOSE: To evaluate clinical outcomes of frozen-thawed embryo transfer cycles when one or two blastocysts are transferred. METHODS: Retrospective chart review RESULTS: Two hundred forty-three frozen blastocyst transfer (FBT) cycles were analyzed. Clinical pregnancy rate (50.4% vs. 34.7%), live birth rate (45.8% vs. 30.6%), and twin live birth rate (19.3% vs. 0) were significantly higher in the double versus single FBT group, respectively (p < 0.05). Prior fresh cycle success with same-cohort embryos did not predict outcome of FBT cycle. When the fresh cycle was unsuccessful, there still was a significant increase in twinning when two frozen-thawed blastocysts were transferred. CONCLUSIONS: Transferring two blastocysts during an FBT cycle resulted in higher live birth and twin live birth rates. Single FBT provided acceptable pregnancy rates for couples seeking to avoid a multiple pregnancy or for those having a single blastocyst stored. Interestingly, the outcome of fresh cycle with same-cohort embryos did not influence the outcome of frozen-thawed cycle.

Pronuclear embryo cryopreservation experience: outcomes for reducing the risk of ovarian hyperstimulation syndrome and for fertility preservation in cancer patients.

PURPOSE: To evaluate pregnancy rate (PR) and live birth rate (LBR) after freezing pronuclear (PN) embryos for two purposes: to reduce the risk of ovarian hyperstimulation syndrome (OHSS) and to bank embryos for cancer patients anticipating gametotoxic chemotherapy/radiotherapy. METHODS: Data from 3,621 consecutive IVF cycles were retrospectively analyzed. PN freezing was offered to patients at risk for OHSS and for those wishing to preserve fertility prior to cancer therapy. Primary outcomes evaluated were PR and LBR. Outcomes were compared to patients who underwent fresh embryo transfer (ET) in 2006. RESULTS: Sixty-six patients froze PN embryos. Thirty-eight were at risk for OHSS. The LBR was 34.3% after one transfer, and 51.4% after a mean of 1.4 transfers. Twenty-eight cancer patients froze embryos. The LBR was 16.7% after one transfer and 25.0% after a mean of 1.5 transfers. The LBR was 35.5% for patients who underwent fresh ET. CONCLUSION: PN freezing with delayed ET is an effective tool for achieving pregnancy for patients at risk of OHSS and for cancer patients wishing to preserve fertility.

Impact of transfer time on pregnancy outcomes in frozen-embryo transfer cycles.

OBJECTIVE: To identify the impact of embryo transfer time (total seconds from the loading of the transfer catheter to the expulsion of the embryo(s) into the uterine cavity) on clinical pregnancy (CPR), implantation (IR), and live birth (LBR) rates. DESIGN: Retrospective cohort study. SETTING: Academic hospital practice. PATIENT(S): A total of 465 women undergoing 571 frozen-embryo transfers with the use of cryopreserved blastocysts in a single academic institution from 2007 through 2014. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): CPR, IR, and LBR. RESULT(S): The cohort was divided into tertiles according to transfer time in seconds (T1: 33-55; T2: 57-81; T3: 82-582) with mean (SD) transfer times of 47.4 (5.7), 67.1 (7.3), and 121.9 (55.1) seconds, respectively. Crude CPRs were 43.9%, 48.7%, and 48.7% among the respective tertiles, crude IRs were 36.9%, 39.9%, and 38.6%, and crude LBRs were 34.8%, 39.6%, and 36.0%. In univariate analysis, inferior cohort score, blood inside catheter, difficult mock transfer, and use of an outer sheath were negatively associated with CPR. No association was seen between physician performing the transfer (including fellows) and CPR. In multivariate regression, longer transfer time was not associated with CPR. With T1 as reference, adjusted odds ratios (95% confidence interval) were 1.28 (0.77-2.11) and 1.52 (0.85-2.71) for transfer time groups T2 and T3, respectively. CONCLUSION(S): After adjusting for potential confounders, this analysis found that contrary to commonly held belief, longer embryo transfer times do not negatively affect CPR, IR, or LBR.

Selective use of percutaneous testis biopsy to optimize IVF-ICSI outcomes: a case series.

BACKGROUND: Sperm quality may degrade during transit through the male reproductive tract in some individuals. In this setting surgically retrieved testicular sperm may outperform ejaculated samples for use with in vitro fertilization (IVF) and intracytoplasmic sperm injection (IVF-ICSI). We sought to describe one center's experience with the use of fresh testicular sperm after prior failed IVF-ICSI with ejaculated samples. RESULTS: A retrospective review was conducted evaluating IVF-ICSI cycles performed at a tertiary IVF unit between 2009 and 2014. Couples who were managed with percutaneous testis biopsy to obtain sperm, despite availability of ejaculated sperm, were included. Four couples who underwent a total of 6 percutaneous testis biopsy/IVF-ICSI cycles were identified. Collectively, the couples had undergone 9 prior IVF-ICSI cycles using fresh ejaculated sperm without successful pregnancy. From the six cycles that used fresh testicular sperm four live births resulted (1 twin gestation, 3 singletons). Only 1 of the 4 couples remained childless. CONCLUSIONS: For patients who have had prior failed IVF-ICSI attempts, this small case series demonstrates a possible therapeutic benefit when freshly procured testicular sperm are used in lieu of ejaculated samples.

Serum 25-hydroxyvitamin D concentrations and treatment outcomes of women undergoing assisted reproduction.

BACKGROUND: Vitamin D deficiency impairs fertility in animal models, but the role of vitamin D in human fertility or treatment of infertility is less clear. OBJECTIVE: We examined the association between circulating 25-hydroxyvitamin D [25(OH)D] concentrations and the outcome in women undergoing assisted reproduction technologies (ARTs). DESIGN: We randomly selected 100 women undergoing infertility treatment with ART enrolled in an ongoing prospective cohort study who underwent 168 treatment cycles. Serum 25(OH)D concentrations were measured in samples collected from women between days 3 and 9 of gonadotropin treatment. Generalized linear mixed models were used to evaluate the association of 25(OH)D concentrations with ART outcomes while adjusting for potential confounders and accounting for repeated treatment cycles per woman. RESULTS: Median (range) serum 25(OH)D concentrations were 86.5 (33.5-155.5) nmol/L. Ninety-one percent of participants consumed multivitamins. Serum 25(OH)D concentrations were positively related to fertilization rate. The adjusted fertilization rate for women in increasing quartiles of serum 25(OH)D were 0.62 (95% CI: 0.51, 0.72), 0.53 (95% CI: 0.43, 0.63), 0.67 (95% CI: 0.56, 0.76), and 0.73 (95% CI: 0.63, 0.80), respectively (P-trend = 0.03). This association persisted when analyses were restricted to women with serum 25(OH)D between 50 and 125 nmol/L when models were further adjusted for season of blood draw and when analyses were restricted to the first treatment cycle. However, 25(OH)D concentrations were unrelated to probability of pregnancy (P-trend = 0.83) or live birth after ART (P-trend = 0.47). CONCLUSION: Vitamin D may be associated with higher fertilization rates, but this apparent benefit does not translate into higher probability of pregnancy or live birth. This trial was registered at www.clinicaltrials.gov as NCT00011713.

Hair mercury concentrations and in vitro fertilization (IVF) outcomes among women from a fertility clinic.

Total hair mercury (Hg) was measured among 205 women undergoing in vitro fertilization (IVF) treatment and the association with prospectively collected IVF outcomes (229 IVF cycles) was evaluated. Hair Hg levels (median=0.62ppm, range: 0.03-5.66ppm) correlated with fish intake (r=0.59), and exceeded the recommended EPA reference of 1ppm in 33% of women. Generalized linear mixed models with random intercepts accounting for within-woman correlations across treatment cycles were used to evaluate the association of hair Hg with IVF outcomes adjusted for age, body mass index, race, smoking status, infertility diagnosis, and protocol type. Hair Hg levels were not related to ovarian stimulation outcomes (peak estradiol levels, total and mature oocyte yields) or to fertilization rate, embryo quality, clinical pregnancy rate or live birth rate.

Soy food intake and treatment outcomes of women undergoing assisted reproductive technology.

OBJECTIVE: To study the relation of dietary phytoestrogens intake and clinical outcomes of women undergoing infertility treatment with the use of assisted reproductive technology (ART). DESIGN: Prospective cohort study. SETTING: Fertility center. PATIENT(S): A total of 315 women who collectively underwent 520 ART cycles from 2007 to 2013. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation, clinical pregnancy, and live birth rates per initiated cycle. RESULT(S): Soy isoflavones intake was positively related to live birth rates in ART. Compared with women who did not consume soy isoflavones, the multivariable-adjusted odds ratios of live birth (95% confidence interval) for women in increasing categories of soy isoflavones intake were 1.32 (0.76-2.27) for women consuming 0.54-2.63 mg/d, 1.87 (1.12-3.14) for women consuming 2.64-7.55 mg/d, and 1.77 (1.03-3.03) for women consuming 7.56-27.89 mg/d. CONCLUSION(S): Dietary soy intake was positively related to the probability of having a live birth during infertility treatment with ART.

Dietary folate and reproductive success among women undergoing assisted reproduction.

OBJECTIVE: To prospectively evaluate the associations of folate with assisted reproductive technology outcomes within a population in the United States. METHODS: This analysis included women (n=232) in a prospective cohort study at the Massachusetts General Hospital Fertility Center. Diet was assessed before assisted reproductive technology treatment using a validated food frequency questionnaire. Intermediate and clinical endpoints of assisted reproductive technology were abstracted from medical records. Generalized linear mixed models with random intercepts to account for multiple cycles per woman were used to evaluate the association of folate intake with assisted reproductive technology outcomes adjusting for calorie intake, age, body mass index, race, smoking status, infertility diagnosis, and protocol type. RESULTS: Among the 232 women (median age 35.2 years, median folate intake 1,778 micrograms/day), higher folate intake was associated with higher rates of implantation, clinical pregnancy, and live birth. The adjusted percentage (95% confidence interval [CI]) of initiated assisted reproductive technology cycles resulting in a live birth for women in increasing quartiles of folate intake were 30% (95% CI 21-42%), 47% (95% CI 35-59%), 42% (95% CI 30-35%) and 56% (95% CI 43-67%) (P for trend=0.01). Live birth rates were 20% (95% CI 8-31%) higher among women in the highest quartile of supplemental folate intake (more than 800 micrograms/day) than among women in the lowest quartile (less than 400 micrograms/day). Higher supplemental folate intake was associated with higher fertilization rates and lower cycle failure rates before embryo transfer (P for trend=0.03 and 0.02). CONCLUSION: Higher intake of supplemental folate was associated with higher live birth rates after assisted reproductive technology treatment. LEVEL OF EVIDENCE: : II.

Pregnancies of unknown location after in vitro fertilization: minimally invasive management with Karman cannula aspiration.

OBJECTIVE: To describe a standardized protocol for the assessment of asymptomatic patients with pregnancies of unknown location (PUL) after IVF. DESIGN: Retrospective cohort study. SETTING: University-based infertility clinic. PATIENT(S): Women undergoing fresh IVF/intracytoplasmic sperm injection (ICSI) cycles between 2005 and 2011. INTERVENTION(S): Endometrial sampling using Karman suction cannula in patients with PUL and abnormal ß-hCG trend (increase <53% or decrease <15% in 2 days) and a pelvic ultrasound unremarkable for an intrauterine pregnancy (IUP) or an ectopic pregnancy (EP). MAIN OUTCOME MEASURE(S): Proportion of patients spared methotrexate (MTX) administration. RESULT(S): Endometrial sampling was performed in 45 patients. Of these, 31 (68.9%) were diagnosed with failed IUP by either a sampling after the ß-hCG decline (≥15%) and/or the presence of villi on final pathology. No further intervention was required. Fourteen patients (31.1%) were diagnosed with presumed EP by persistent ß-hCG level after negative pathology. Ten of these patients (71%) were successfully treated with a single dose of MTX; three required an additional dose, and one required laparoscopy for a ruptured EP. CONCLUSION(S): In asymptomatic patients with PUL and abnormal ß-hCG trends after IVF, the utility of Karman aspiration to confirm an IUP may obviate treatment with MTX in more than two-thirds of patients.

Elective cryopreservation of all embryos with subsequent cryothaw embryo transfer in patients at risk for ovarian hyperstimulation syndrome reduces the risk of adverse obstetric outcomes: a preliminary study.

OBJECTIVE: To test the hypothesis that patients who undergo elective cryopreservation of all embryos, due to risk of ovarian hyperstimulation syndrome and elevated peak serum estradiol (E(2)), previously defined as level >3,450 pg/mL (90th percentile) during in vitro fertilization (IVF), will be less likely to have small for gestational age (SGA) infants and preeclampsia as compared with patients with elevated peak serum E(2) who undergo fresh embryo transfer (ET). DESIGN: Cohort study. SETTING: Tertiary care academic medical center. PATIENT(S): Twenty women who underwent elective cryopreservation of all embryos with subsequent cryothaw ET and 32 similar women with elevated peak E(2) during controlled ovarian hyperstimulation for IVF who underwent a fresh ET. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Prevalence of SGA infants and development of preeclampsia in patients with cryothaw ET or fresh ET in the setting of elevated peak E(2). RESULT(S): After adjusting for confounders (body mass index, antral follicle count, peak serum E(2) level) using forward stepwise logistic regression, the patients who elected cryopreservation of all embryos and subsequent cryothaw ET were statistically significantly less likely to deliver SGA infants as compared with the patients who had fresh ET in the setting of elevated peak E(2). In the entire cohort, a total of seven women had preeclampsia, all of whom had had fresh ET in the setting of elevated peak serum E(2): 7 (21.9%) in the fresh ET group versus 0 women in the elective cryopreservation group. CONCLUSION(S): This preliminary study suggests that elective cryopreservation of all embryos in patients with elevated peak serum E(2) for subsequent cryothaw ET in cycles with a better physiologic hormonal milieu may reduce the odds of SGA and preeclampsia in IVF singleton deliveries.

Men's body mass index in relation to embryo quality and clinical outcomes in couples undergoing in vitro fertilization.

OBJECTIVE: To evaluate the association between men's body mass index (BMI), early embryo quality, and clinical outcomes in couples undergoing in vitro fertilization (IVF). DESIGN: Prospective cohort study. SETTING: Fertility clinic in an academic medical center. PATIENT(S): 114 couples who underwent 172 assisted reproduction cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fertilization rate, embryo quality, implantation rate, clinical pregnancy rate, and live birth rate. RESULT(S): The fertilization rate was higher among obese men than among normal weight men in conventional IVF cycles. No statistically significant associations were found between men's BMI and the proportion of poor-quality embryos on day 3, slow embryo cleavage rate, or accelerated embryo cleavage rate. Men's BMI was unrelated to positive ß-human chorionic gonadotropin rate, clinical pregnancy rate, or live-birth rate per embryo transfer. Among couples undergoing intracytoplasmic sperm injection, the odds of live birth in couples with obese male partners was 84% lower than the odds in couples with men with normal BMI. CONCLUSION(S): Our data suggest a possible deleterious effect of male obesity on the odds of having a live birth among couples undergoing intracytoplasmic sperm injection.

Body mass index and short-term weight change in relation to treatment outcomes in women undergoing assisted reproduction.

OBJECTIVE: To assess the relation between body mass index (BMI) and short-term weight change with assisted reproductive technology (ART) outcomes. DESIGN: Prospective cohort study. SETTING: Fertility center. PATIENT(S): A total of 170 women undergoing 233 ART cycles. INTERVENTION(S): Baseline BMI and short-term weight change were related to ART outcomes. Regression models accounting for repeated observations were used to adjust data for potential confounders. MAIN OUTCOME MEASURE(S): Peak E2 levels, oocyte yield, MII yield, fertilization rate, embryo quality, postive [beta]-hCH, clinical pregnancy and live birth rates. RESULT(S): Overweight and obesity were associated with lower live birth rates. The adjusted live birth rate (95% confidence interval) was 42% (28%-58%) among women with a BMI between 20 and 22.4 kg/m(2) and 23% (14%-36%) among overweight or obese women. Short-term weight loss was associated with a higher proportion of metaphase II (MII) oocytes retrieved. The adjusted proportion of MII eggs was 91% (87%-94%) for women who lost 3 kg or more and 86% (81%-89%) for women whose weight remained stable. This association was stronger among women who were overweight or obese at baseline. Short-term weight loss was unrelated to positive ß-hCG, clinical pregnancy, or live birth rates. CONCLUSION(S): Overweight and obesity were related to lower live birth rates in women undergoing ART. Short-term weight loss was related to higher MII yield, particularly among overweight and obese women, but unrelated to clinical outcomes.

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.

OBJECTIVE: To assess the impact of elevated peak serum E(2) levels (EPE(2); 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 EPE(2). RESULT(S): Patients with EPE(2) 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 EPE(2) and the likelihood for delivery before 37 weeks, 35 weeks, or 32 weeks of gestation. Receiver operating characteristic analysis revealed that EPE(2) level predicted adverse obstetrical outcome (SGA + PreE) with 38.5% and 91.7% sensitivity and specificity, respectively. Using a serum peak E(2) 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): EPE(2) 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.

In vitro maturation (IVM) of murine and human germinal vesicle (GV)-stage oocytes by coculture with immortalized human fallopian tube epithelial cells.

OBJECTIVE: To improve the maturation rate of murine and human germinal vesicle (GV) oocytes using human tubal epithelial cells (hTECs). DESIGN: Murine and human GV oocytes were randomized to human tubal fluid (HTF) media alone or cocultured with mouse embryonic fibroblasts (MEFs) or primary hTECs or immortalized hTECS (ihTECs) for various times. Rates of maturation to meiosis II (MII) were compared between groups. INTERVENTION(S): TECs were isolated from discarded salpingectomy specimens. One batch was immortalized with TERT and SV40 large T-antigen. GV oocytes (n = 710) were isolated from 8-week-old-mice at 40 hours after pregnant mare's serum gonadotropin stimulation. Discarded human GV oocytes (n = 62) were obtained from intracytoplasmic sperm injection cycle IVF center patients. Oocytes were cultured in HTF media alone or with MEFs, hTECs, or ihTECs. MAIN OUTCOME MEASURE(S): Maturation rates were assessed by standard morphological criteria and compared. RESULT(S): The maturation rate of murine GV oocytes to MII at 12 and 24 hours increased significantly in coculture with hTECS and ihTECS compared with MEF and HTF media alone. In addition, the development rate after IVF was significantly higher with hTECS and ihTECS than in MEF and HTF media alone. Maturation of human GV oocytes to MII at 24 and 48 hours was significantly higher in hTECS and ihTECS compared with HTF media alone. CONCLUSION(S): Coculture with either primary or immortalized TECs might improve oocyte quality and significantly raise in vitro maturation rates for GV oocytes.

Body mass index in relation to semen quality, sperm DNA integrity, and serum reproductive hormone levels among men attending an infertility clinic.

OBJECTIVE: To examine the association between body weight and measures of male reproductive potential. DESIGN: Cross-sectional study. SETTING: Fertility clinic in an academic medical center. PATIENT(S): Four hundred eighty-three male partners of subfertile couples. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Standard semen analysis, sperm DNA fragmentation, and serum levels of reproductive hormones. RESULT(S): As expected, body mass index (BMI) was positively related to estradiol levels and inversely related to total testosterone and sex hormone-binding glogulin (SHBG) levels. There was also a strong inverse relation between BMI and inhibin B levels and a lower testosterone:LH ratio among men with a BMI > or = 35 kg/m(2). Body mass index was unrelated to sperm concentration, motility, or morphology. Ejaculate volume decreased steadily with increasing BMI levels. Further, men with BMI > or = 35 kg/m(2) had a lower total sperm count (concentration x volume) than normal weight men (adjusted difference in the median [95% confidence interval] = -86 x 10(6) sperm [-134, -37]). Sperm with high DNA damage were significantly more numerous in obese men than in normal-weight men. CONCLUSION(S): These data suggest that despite major differences in reproductive hormone levels with increasing body weight, only extreme levels of obesity may negatively influence male reproductive potential.

Semen quality and sperm DNA damage in relation to urinary bisphenol A among men from an infertility clinic.

Bisphenol A (BPA) impairs spermatogenesis in animals, but human studies are lacking. We measured urinary BPA concentrations, semen quality, and sperm DNA damage (comet assay) in 190 men recruited through an infertility clinic. BPA was detected in 89% of samples, with a median (interquartile range [IQR]) concentration of 1.3 (0.8-2.5) ng/mL. Urinary BPA concentration was associated with slightly elevated, though not statistically significant, odds for below reference sperm concentration, motility, and morphology. When modeled as continuous dependent variables, an IQR increase in urinary BPA concentration was associated with declines in sperm concentration, motility, and morphology of 23% (95%CI -40%, -0.3%), 7.5% (-17%, +1.5%), and 13% (-26%, -0.1%), respectively, along with a 10% (0.03%, 19%) increase in sperm DNA damage measured as the percentage of DNA in comet tail. In conclusion, urinary BPA may be associated with declined semen quality and increased sperm DNA damage, but confirmatory studies are needed.