Oocyte Cryopreservation: A 9-Year Single-Centre Experience.

OBJECTIVE: Oocyte cryopreservation (OC) has increased in recent years; however, there is a paucity of published data on the use of cryopreserved oocytes and associated outcomes. METHODS: A retrospective review of 748 OC cycles between 2013 and 2022 at a private fertility centre was performed. Outcome parameters for oocyte retrieval cycles were reviewed. For patients who returned for oocyte disposition, outcomes subsequent to oocyte re-warming, fertilization, and transfer were analyzed. RESULTS: There were 748 OC cycles (653 elective and 95 non-elective) in 646 patients (556 elective and 90 non-elective). Patients were older at the time of freezing in the elective oocyte group compared with the non-elective group (36.5 vs. 28.8 y; P < 0.001). Sixty-five patients returned to warm and fertilize their oocytes (50 in the elective group and 15 in the non-elective group). The survival rate for warmed oocytes was 76.1% (541/711), and 66.2% of surviving oocytes were successfully fertilized, and 39.1% reached blastulation. Twenty-three patients underwent embryo transfers (10 after preimplantation genetic testing for aneuploidy), with 15 patients having at least 1 delivery or ongoing pregnancy. CONCLUSIONS: To date, this is the largest published experience with OC in Canada. OC can lead to successful live births but does not guarantee a viable outcome for all patients. In this study, most patients with vitrified oocytes had not returned for disposition, so long-term follow-up is still required to verify the efficacy of OC.

GnRH triggering may improve euploidy and live birth rate in hyper-responders: a retrospective cohort study.

PURPOSE: Despite the increasing use of GnRHa to trigger final oocyte maturation in segmented IVF cycles, the effects of trigger modality on chromosomal competence and embryo quality remain controversial. Hence, the purpose of this study was to compare euploidy rates and pregnancy outcomes among hyper-responding women using hCG versus GnRHa trigger. METHODS: This retrospective study included 333 hyper-responders, defined as >15 oocytes retrieved, who underwent preimplantation genetic testing (PGT-A) in segmented IVF cycles using either GnRHa or urinary hCG trigger. Live birth rate (LBR) was the primary outcome of interest. Implantation rate (IR), clinical pregnancy rate (CPR), and euploidy rate were secondary outcomes. RESULTS: GnRH triggering was associated with improved IR (70.5 vs. 53.2%, p = 0.0475), LBR (51.3 vs. 33.8%, p = 0.0170) compared to hCG. A greater number of oocytes were retrieved (21.9 vs 18.4%, p < 0.001) and euploid embryos produced (2.8 vs. 2.1, p = 0.0109) after GnRHa triggering, while higher euploidy rates were only observed among women <35-years-old (62.0 vs. 51.7%, p = 0.0307) using GnRHa trigger. Higher OHSS rates were observed after hCG triggering (10.6 vs. 2.1%, p = 0.0009). CONCLUSION: Hyper-responders who received GnRHa trigger experienced improved pregnancy outcomes and lower rates of OHSS compared to hCG triggering. The higher number of oocytes retrieved and euploid embryos produced may reflect an improved developmental competence using GnRHa triggering due to physiologic induction of both LH and FSH surge or other undefined mechanisms that improve embryo development. However, higher overall euploid rates were only observed among women <35-years-old using the GnRHa trigger. Further prospective studies are required to validate this observation and evaluate the specific influence of different ovulation triggers on gamete developmental competence among hyper-responder women.

Analysis of PGT-M and PGT-SR outcomes at a Canadian fertility clinic.

OBJECTIVE: Outcomes from in vitro fertilization (IVF)/intrauterine insemination (ICSI) cycles for patients who underwent preimplantation genetic testing for monogenic/single gene (PGT-M) and structural chromosome rearrangements (PGT-SR) patients were reviewed. Patients pursuing PGT-M and PGT-SR often do not have pre-existing fertility issues and therefore may have uncertain expectations of successful outcomes. Before pursuing PGT-M and PGT-SR, patients require evidence-based counseling regarding the probability of having a healthy child. METHOD: Retrospective review from a single private IVF clinic of 73 PGT patients, from whom a total of 437 blastocysts were biopsied and screened. Embryo results and pregnancy outcomes were analyzed. RESULTS: Of the 45 PGT-M patients, 64.4% had at least one euploid unaffected embryo. The cumulative pregnancy rate for patients who had embryo transfers in this group was 89.7%, with an ongoing pregnancy or delivery rate of 48.9%. For the 28 PGT-SR patients, 60.7% had at least one euploid unaffected embryo. The cumulative pregnancy rate for patients who had embryo transfers in this group was 87.5%, with an ongoing pregnancy or delivery rate of 42.9%. CONCLUSION: This information can supplement the existing data in the literature to counsel new patients in terms of realistic expectations of success following PGT-M and PGT-SR.

Measurement of Luteinizing Hormone Level After Gonadotropin-Releasing Hormone Agonist Trigger Is Not Useful for Predicting Oocyte Maturity.

OBJECTIVE: To study whether the measurement of LH after GnRH agonist trigger is correlated with the proportion of mature oocytes. METHODS: We performed a retrospective cohort study at a private, university-affiliated fertility centre in Vancouver, BC. Patients who underwent IVF/ICSI cycles and used a GnRH agonist trigger were included. Serum LH levels were measured on the day of trigger and one day later. The main study outcome measure was the proportion of mature oocytes. RESULTS: Including all 97 cycles in the cohort, the average post-trigger LH level was 69.3 IU/L (10.5-133.3 IU/L) and the average rise was 66.8 IU/L (10.0-129.4 IU/L). The mean number of oocytes collected was 17 and, on average, 82% were mature. We did not find any association between post-trigger LH levels (r = 0.004, P = 0.968) or rise in LH level (r = 0.01, P = 0.92) and the proportion of mature oocytes collected. The percentage rise in LH level was also not predictive of the proportion of mature oocytes in the estradiol and oral contraceptive pill groups separately (estradiol r = 0.118, OCP r = 0.07; P > 0.05) or together (r = 0.1, P = 0.34). CONCLUSION: Neither the absolute post-trigger LH level nor the rise in LH level is predictive of the proportion of mature oocytes collected. Taken together with the excellent response to GnRH agonist trigger evidenced by the average oocyte maturity, we do not believe it is necessary to measure post-trigger LH levels.

A pilot study to investigate the clinically predictive values of copy number variations detected by next-generation sequencing of cell-free deoxyribonucleic acid in spent culture media.

OBJECTIVE: To investigate the positive predictive value and false positive risk of copy number variations (CNV's) detected in cell free deoxyribonucleic acid (DNA) from spent culture media for nonviable or aneuploid embryos. DESIGN: Diagnostic/prognostic accuracy study. PATIENT(S): Patients aged 35 and younger with an indication for IVF-ICSI and elective single frozen embryo transfer at a single, private IVF center. INTERVENTION: Embryo selection was performed according to the conventional grading, blinded to noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) results. After clinical outcomes were established, spent culture media samples were analyzed. MAIN OUTCOME MEASURES: Prognostic accuracy of CNVs according to niPGT-A results to predict nonviability or clinical aneuploidy. RESULTS: One hundred twenty patients completed the study. Interpretations of next-generation sequencing (NGS) profiles were as follows: 7.5% (n = 9) failed quality control; 62.5% (n = 75) no CNVs detected; and 30% (n = 36) abnormal copy number detected. Stratification of abnormal NGS profiles was as follows: 15% (n = 18) whole chromosome and 15% (n = 18) uncertain reproductive potential. An intermediate CNV was evident in 27.8% (n = 5) of the whole chromosome abnormalities. The negative predictive value for samples with no detected abnormality was 57.3% (43/75). Whole chromosome abnormality was associated with a positive predictive value of 94.4% (17/18), lower sustained implantation rate (5.6%, 1/18), and higher relative risk (RR) for nonviability compared with no detected abnormalities (RR 2.21, 95% CI: 1.66-2.94). No other CNVs were associated with significant differences in the sustained implantation or RRs for nonviability. Unequal sex chromosome proportions suggested that maternal contamination was not uncommon. A secondary descriptive analysis of 705 supernumerary embryos revealed proportions of NGS profile interpretations similar to the transferred cohort. Significant median absolute pairwise differences between certain subcategories of CNV abnormalities were apparent. CONCLUSION: Whole chromosome abnormalities were associated with a high positive predictive value and significant RR for nonviability. Embryos associated with other CNVs had sustained implantation rates similar to those with no abnormalities detected. Further studies are required to validate the clinical applicability of niPGT-A. CLINICAL TRIAL REGISTRATION NUMBER: clinicaltrials.gov (NCT04732013).

At-home urine estrone-3-glucuronide quantification predicts oocyte retrieval outcomes comparably with serum estradiol.

Objective: To investigate the feasibility of monitoring urine estrone-3-glucuronide (E3G) with an at-home device during gonadotropin stimulation for in vitro fertilization and oocyte cryopreservation. Design: Prospective, observational cohort study. Setting: Private fertility clinic. Patients: Thirty patients undergoing stimulation with a gonadotropin-releasing hormone antagonist protocol for in vitro fertilization or oocyte cryopreservation. Interventions: Daily collection of the first urine in the morning during stimulation and analysis performed at home by each patient with the Mira Fertility Tracker. Main Outcome Measures: Primary outcomes were correlation of urine E3G and serum estradiol (E2) concentrations on the day of trigger to the number of total and metaphase 2 oocytes (MII). Secondary outcomes of interest were the correlation of matched E3G and E2 measurements and the daily trends of E3G and E2 during stimulation. Results: Both urine E3G and serum E2 concentrations on the day of trigger significantly correlated with retrieval outcomes to a similar extent, with E3G demonstrating slightly higher correlation to the number of MII oocytes than that demonstrated by E2 (r = 0.485 vs. 0.391, respectively). The Pearson correlation coefficient for matched E3G and E2 levels was 0.761. The correlation coefficients of determination for daily trends of E3G and E2 during stimulation were 0.7066 and 0.6102, respectively. Conclusions: Measured on the day of trigger, urine E3G monitoring during gonadotropin stimulation was comparable with serum E2 for predicting oocyte retrieval outcomes. Matched daily samples confirmed good correlation of urine E3G and serum E2. The option of at-home estrogen monitoring with devices such as Mira offers an alternative to traditional serum monitoring that may improve patient experience. Clinical Trial Registration Number: NCT05493202.

Anti-Müllerian hormone testing is useful for individualization of stimulation protocols in oocyte donors.

While the age of a donor is a fundamental factor to the success of donor IVF, no serum markers have been demonstrated to be useful in predicting variability of ovarian response in individual donors. Anti-Müllerian hormone (AMH) has been described as an accurate marker of ovarian response in patients undergoing IVF, but has not been applied to oocyte donors. AMH concentrations from 104 anonymous oocyte donors between the ages of 21-32 years were studied and IVF outcome parameters compared. AMH was correlated with several parameters including the number of oocytes retrieved (r = 0.232, P = 0.024), the peak oestradiol concentrations (r = 0.235, P = 0.024) and the need to decrease gonadotrophin dose in order to avoid ovarian hyperstimulation syndrome (r = 0.274, P = 0.007). Receiver operating curve analysis was able to identify an AMH threshold that rendered about 70% sensitivity and 70% specificity for predicting the need to decrease gonadotrophin dosing. The clinical pregnancy rate was 77% per recipient and was not related to the donors' AMH concentrations. For oocyte donors, measurement of AMH appears most useful for determining gonadotrophin sensitivity in order to mitigate symptoms consistent with ovarian hyperstimulation.

Anti-Müllerian hormone testing is useful for individualization of stimulation protocols in oocyte donors.

While the age of a donor is a fundamental factor to the success of donor IVF, no serum markers have been demonstrated to be useful in predicting variability of ovarian response in individual donors. Anti-Müllerian hormone (AMH) has been described as an accurate marker of ovarian response in patients undergoing IVF, but has not been applied to oocyte donors. AMH concentrations from 104 anonymous oocyte donors between the ages of 21-32 years were studied and IVF outcome parameters compared. AMH was correlated with several parameters including the number of oocytes retrieved (r=0.232, P=0.024), the peak oestradiol concentrations (r=0.235, P=0.024) and the need to decrease gonadotrophin dose in order to avoid ovarian hyperstimulation syndrome (r=0.274, P=0.007). Receiver operating curve analysis was able to identify an AMH threshold that rendered about 70% sensitivity and 70% specificity for predicting the need to decrease gonadotrophin dosing. The clinical pregnancy rate was 77% per recipient and was not related to the donors' AMH concentrations. For oocyte donors, measurement of AMH appears most useful for determining gonadotrophin sensitivity in order to mitigate symptoms consistent with ovarian hyperstimulation.

The association between anti-Müllerian hormone and IVF pregnancy outcomes is influenced by age.

The conflicting results from studies on the predictive capabilities of serum anti-Müllerian hormone (AMH) for IVF pregnancy outcomes may be attributed to small sample sizes and disparities in the age of the study populations. The relationship between AMH and IVF pregnancy outcomes was clarified with retrospective cross-tabulation analyses (n=1558) stratified by age to control for its confounding effects. Serum AMH concentrations were divided into tertiles (≤ 0.29, 0.30-1.20, ≥ 1.21 ng/ml) and ages into four groups (<34, 34-37, 38-41, ≥ 42 years). For women <34, having serum AMH in the lowest tertile did not reduce the chance of IVF pregnancy/live birth compared with those with higher AMH concentrations. For women 34-41, a significant positive relationship existed between serum AMH and pregnancy rates. For women ≥ 42, serum AMH concentrations ≤ 0.29 ng/ml were associated with a 3% chance of pregnancy, and women with AMH ≥ 1.21 ng/ml had the same pregnancy rate as women with concentrations 0.30-1.20 ng/ml. In conclusion, AMH has limited predictive value for IVF outcomes in the two extremes of female reproductive age; however, for women between 34 and 41, higher serum AMH concentrations are associated with significantly greater chances of pregnancy (P<0.01).

Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial.

OBJECTIVE: To evaluate the benefit of next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) for embryo selection in frozen-thawed embryo transfer. DESIGN: Randomized controlled trial. SETTING: Not applicable. PATIENT(S): Women aged 25-40 years undergoing IVF with at least two blastocysts that could be biopsied. INTERVENTION(S): Randomization for single frozen-thawed embryo transfer with embryo selection based on PGT-A euploid status versus morphology. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate (OPR) at 20 weeks' gestation per embryo transfer. RESULT(S): A total of 661 women (average age 33.7 ± 3.6 years) were randomized to PGT-A (n = 330) or morphology alone (n = 331). The OPR was equivalent between the two arms, with no significant difference per embryo transfer (50% [137/274] vs. 46% [143/313]) or per intention to treat (ITT) at randomization (41.8% [138/330] vs. 43.5% [144/331]). Post hoc analysis of women aged 35-40 years showed a significant increase in OPR per embryo transfer (51% [62/122] vs. 37% [54/145]) but not per ITT. CONCLUSION(S): PGT-A did not improve overall pregnancy outcomes in all women, as analyzed per embryo transfer or per ITT. There was a significant increase in OPR per embryo transfer with the use of PGT-A in the subgroup of women aged 35-40 years who had two or more embryos that could be biopsied, but this was not significant when analyzed by ITT. CLINICAL TRIAL REGISTRATION NUMBER: NCT02268786.

Frequencies of chromosome-specific mosaicisms in trophoectoderm biopsies detected by next-generation sequencing.

OBJECTIVE: To examine the chromosome-specific frequencies of mosaicism detected by next-generation sequencing (NGS) compared with constitutional aneuploidy. DESIGN: Retrospective cross-sectional review of NGS results from trophectoderm biopsies analyzed by per-chromosome prevalence of mosaicism and constitutional aneuploidy. SETTING: Private fertility clinic. PATIENT(S): A total of 378 patients who underwent preimplantation genetic screening by NGS for routine clinical indications from February 2016 to April 2017. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Aneuploidies and mosaicisms were tabulated per chromosome, and whole-chromosome and segmental mosaicisms were also analyzed. RESULT(S): NGS results were analyzed from 1,547 blastocysts. Mosaicism was detected as the sole abnormality in 17.5% (n = 270) of samples but were also found in 196/634 aneuploid embryos, so the overall incidence of mosaicism per biopsy was 30.1%. Mosaicism did not statistically vary when stratified by maternal age. The mean rate of overall mosaicism per chromosome was 2.46%. When whole chromosome and segmental mosaicisms were compared, unequal frequencies were found in several chromosomes. Trisomy was more frequently detected as whole-chromosome mosaicism, although monosomy was more frequently seen in segmental mosaicism. Aneuploidy and mosaicism displayed different patterns of distribution in various chromosomes. CONCLUSION(S): Mosaicism is unequally detected in various chromosomes and appears distinct from the distribution pattern of constitutional aneuploidy. Whole chromosome and segmental mosaicisms are also differentially detected. These results contribute to the study of mosaicism, illuminating a differential pattern of detection across the genome.

Müllerian inhibiting substance and disrupted folliculogenesis in polycystic ovary syndrome.

OBJECTIVE: This study determines whether pretreatment levels of müllerian inhibiting substance/antimüllerian hormone (MIS/AMH) would reflect ovarian response to exogenous gonadotropin in women with polycystic ovary syndrome (PCOS) and ovulatory controls matched by age and weight. STUDY DESIGN: Case-control study of 20 women with PCOS and 10 normoovulatory women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) at an academic medical center. RESULTS: Baseline serum MIS/AMH levels in PCOS were higher than those of normoovulatory women (P < .001). MIS/AMH levels increased after gonadotropin-releasing hormone (GnRH) agonist pituitary suppression; 0.5 ng/mL in PCOS (P = .12) and 0.7 ng/mL in controls (P < .02). In normoovulatory women, MIS/AMH at baseline, after pituitary suppression, and the interval change after pituitary suppression all correlated closely to the number of mature oocytes retrieved (P < .005). In PCOS, however, levels of MIS/AMH at baseline and after pituitary suppression did not show this correlation, whereas only the interval change correlated with the number of mature oocytes retrieved. CONCLUSION: Baseline MIS/AMH is a good predictor of the ovarian response to COH in normoovulatory women but not in PCOS.

Inhibition of the vascular endothelial cell (VE)-specific adhesion molecule VE-cadherin blocks gonadotropin-dependent folliculogenesis and corpus luteum formation and angiogenesis.

Although it has been previously demonstrated that administration of anti-vascular endothelial growth factor (VEGF) receptor-2 antibodies to hypophysectomized (Hx) mice during gonadotropin-stimulated folliculogenesis and luteogenesis inhibits angiogenesis in the developing follicle and corpus luteum (CL), it is unclear which of the many components of VEGF inhibition are important for the inhibitory effects on ovarian angiogenesis. To examine whether ovarian angiogenesis can be more specifically targeted, we administered an antibody to VE-cadherin (VE-C), an interendothelial adhesion molecule, to Hx mice during gonadotropin stimulation. In tumor models and in vivo and in vitro assays, the anti-VE-C antibody E4G10 has been shown to specifically inhibit angiogenesis, but VE-C has yet to be inhibited in the context of ovarian angiogenesis. In addition to studying the effect on neovascularization in the follicular and luteal phases, we also examined the effect of E4G10 on established vessels of the CL of pregnancy. The results demonstrate that E4G10 specifically blocks neovascularization in the follicular and luteal phases, causing an inhibition of preovulatory follicle and CL development, a decrease in the vascular area, and an inhibition of function demonstrated by reduced hormone levels. However, when administered during pregnancy, unlike anti-VEGF receptor-2 antibody, E4G10 is unable to cause disruption of the established vessels of the mature CL. These data demonstrate that E4G10 causes a specific inhibition of neovascularization in the ovary without destabilizing preexisting vasculature.

Addressing the growing problem of multiple gestations created by assisted reproductive therapies.

Iatrogenic multiple pregnancy is the most significant complication of assisted reproductive technology (ART). Approximately half of all children born subsequent to ART result from a plural gestation. Furthermore, the majority of triplets and higher order births are the product of ART. The risks for multiple pregnancy vary with practice patterns and the techniques used to achieve pregnancy. Recognizing the potential for serious morbidity associated with multiple pregnancies, infertility specialists have developed strategies to reduce the complication of multiple pregnancies while maintaining acceptable pregnancy rates. Implementation of these refined practices has led to a reduction in the incidence of higher order multiple births, although the incidence of twins has yet to be minimized. Further reduction in the incidence of multiple births after ART necessitates a redefinition of success to emphasize the healthy singleton birth rate, rather than crude pregnancy rates.

Deaths of HIV-positive men in the context of assisted reproduction: five case studies from a single center.

Provision of reproductive services to individuals infected with HIV-1 is gaining popular acceptance and is generally endorsed by specialists in reproductive medicine. In the situation in which the male is HIV positive and the female partner is not infected, a large body of evidence has demonstrated that the use of assisted reproductive technology is effective for achieving pregnancy, while eliminating the risk of viral transmission to the mother and fetus. No reports have documented the well-being of the HIV-infected partners subsequent to seeking fertility services. In the current report, we document the cases of five HIV-positive men who died secondary to complications of HIV infection shortly after participating in the assisted reproduction program for HIV-1-serodiscordant couples at Columbia University. Three of these couples successfully achieved pregnancy and live birth, including one set of triplets, and one case of posthumous conception; the fourth case resulted in the cryopreservation of all embryos after the sudden death of the male before the time of embryo transfer; the fifth couple failed to conceive. None of the deaths, which occurred within a few months to 2 years from initial consultation, were related to infertility treatment. The demographic and social statuses of these patients were not different from the general population of men seeking assisted reproduction in our clinic. Regarding the HIV infection status of these cases, three patients had a longer duration of infection compared to the general population of men in our cohort, and one had a significantly lower CD4 cell count. All five men had stable HIV viral loads, and were determined by their primary care providers to be clinically healthy at the time of entry into the program for assisted reproduction. The untimely deaths of these patients underscores the importance of the thoughtful consideration of the complex issues involved in family planning for these individuals, including advanced directives for the use of cryopreserved gametes and embryos, and the social, emotional, and practical issues for the children and surviving partners subsequent to the death of the HIV-positive parent.

Posthumous assisted reproduction: a survey of attitudes of couples seeking fertility treatment and the degree of agreement between intimate partners.

OBJECTIVE: To study attitudes about posthumous assisted reproduction (PAR) in individuals presenting for assisted reproduction, to examine the degree of concordance of attitudes within couples, and to determine whether individuals can accurately predict the attitudes of their intimate partners. DESIGN: Cross sectional survey. SETTING: University-based fertility center. PATIENT(S): One hundred six couples presenting for an initial fertility evaluation. INTERVENTION(S): Anonymous survey completed independently by each partner. MAIN OUTCOME MEASURE(S): 1) individual attitudes about PAR, 2) the rate of concordance in attitudes within couples, and 3) the ability of individuals to predict their partner's attitudes. RESULT(S): Approximately 78% of individuals stated they would permit PAR. Couples expressed concordant attitudes about 75% of the time. Statistically, women and men were equivalent in correctly predicting their partner's attitudes (79% vs. 71%). CONCLUSION(S): Although most individuals presenting for fertility treatment would agree to PAR, there was also a notable portion that stated that they would not consent with the process. Although most couples had concordant attitudes, discordance was also prevalent. Individuals often, but not always, were able to predict their partner's attitudes about PAR.

Posthumous assisted reproduction.

Cryopreservation of gametes and embryos allows for children to be conceived after the death of their genetic parents through the process of posthumous assisted reproduction (PAR). Although the techniques are routine, the moral and ethical details are controversial and remain unsettled. Furthermore, there are numerous medicolegal implications that complicate matters. The principal parties to be considered are the decedent, the child who will be born of PAR, the significant other requesting the procedure, other living children, and even society at large. Numerous case studies exist and expert opinions have been published recognizing PAR as a vexing ethical issue. Most experts agree that explicit written consent forms signed at the time of cryopreservation are the best method to minimize some of the controversy involved with PAR.

Changes in markers of ovarian reserve and endocrine function in young women with breast cancer undergoing adjuvant chemotherapy.

BACKGROUND: Premenopausal women undergoing chemotherapy are at risk for amenorrhea and impaired fertility. The objective of the current study was to assess levels of mullerian inhibitory substance (MIS), estradiol (E2), follicle-stimulating hormone (FSH), and menstrual status, in women undergoing chemotherapy. METHODS: A nested prospective cohort study was conducted in women aged <40 years with breast cancer (BC) who were undergoing adjuvant chemotherapy (n = 26). Serum MIS, FSH, and E2 were measured before chemotherapy (baseline) and at Weeks 6, 12, 36, and 52. Controls were 134 age-matched women with known fertility. Hormone levels were compared between the cases and controls at baseline. Differences between amenorrhea and age subgroups were tested using the nonparametric Wilcoxon 2-sample test using a 2-sided alpha of 0.05. RESULTS: Subjects with BC and age-matched controls had similar baseline MIS levels (median, 0.94 ng/mL vs 0.86 ng/mL;, P > .05). Serum MIS decreased significantly at 6 weeks and remained suppressed for 52 weeks. E2 levels decreased, and FSH levels increased during chemotherapy; however, at 52 weeks, the levels returned to baseline. At 52 weeks, only 1 patient had MIS above the lower normal range, 15 had return of menstrual function, 11 had premenopausal levels of FSH, and 13 had follicular phase levels of E2. In women aged <35 years, 25% remained amenorrheic, whereas in women aged >35 years, 50% were amenorrheic. Amenorrheic and menstruating women were found to have similar MIS values at baseline and follow-up. CONCLUSIONS: In young women with BC, chemotherapy decreases MIS rapidly and dramatically. Rapid reductions in MIS do not appear to be predictive of subsequent menstrual function. Ovarian reserve and endocrine function may be affected differently by chemotherapy.

Providing fertility care to men seropositive for human immunodeficiency virus: reviewing 10 years of experience and 420 consecutive cycles of in vitro fertilization and intracytoplasmic sperm injection.

OBJECTIVE: To review 10 years of experience providing fertility care to men seropositive for human immunodeficiency virus (HIV) using sperm washing and in vitro fertilization with intracytoplasmic sperm injection (IVF-ICSI). DESIGN: Retrospective study. SETTING: University-based practice. PATIENT(S): HIV-seropositive men with HIV-seronegative partners. INTERVENTION(S): IVF-ICSI, HIV testing of females and infants. MAIN OUTCOME MEASURE(S): IVF performance, pregnancy rates, obstetrical outcomes, infection rates. RESULT(S): We initiated 420 cycles (355 fresh and 65 frozen cycles) in 181 couples. Due to poor ovarian response, 16% of stimulations were canceled. The number of oocytes collected per retrieval was 15.0 +/- 0.5, providing 12.1 +/- 0.5 mature oocytes suitable for ICSI, yielding 9.0 +/- 0.3 embryos per couple. The overall clinical pregnancy rate/embryo transfer was 45%; ongoing/delivered pregnancy rate/embryo transfer was 37%. The most frequent obstetric complication was multiple gestation (41%), with 5% experiencing high order multiple birth. An attendant high rate of preterm delivery was noted, as 43% of infants were born premature. No maternal or neonatal HIV infections or deaths occurred. CONCLUSION(S): We have found IVF-ICSI to be an expeditious and safe means for HIV-serodiscordant couples to achieve pregnancy with minimal risk of viral infection. Risks and liabilities of IVF-ICSI relate to multiple gestations and will occur in a significant number of participants.