Obstetric and Neonatal Outcomes After Transferring More Than One Embryo in Patients With Preimplantation Genetic Testing.

OBJECTIVE: To compare obstetric and neonatal outcomes after single embryo transfer (SET) compared with multiple embryo transfer (MET) from frozen-thawed transfer cycles of embryos that underwent preimplantation genetic testing for aneuploidies (PGT-A). METHODS: We conducted a retrospective cohort study from the SART CORS (Society for Assisted Reproductive Technology Clinic Outcome Reporting System) national database. Clinical and demographic data were obtained from the SART CORS database for all autologous and donor egg frozen-thawed transfer cycles of embryos that underwent PGT-A between 2014 and 2016, after excluding cycles that used frozen oocytes, fresh embryo transfer, and transfers of embryos from more than one stimulation cycle. Multivariable linear and log-binomial regression models were used to estimate the relative and absolute difference in live-birth rate, multiple pregnancy rate, gestational age at delivery, and birth weight between SET compared with MET. RESULTS: In total, 15,638 autologous egg transfer cycles and 944 donor egg transfer cycles were analyzed. Although the live-birth rate was higher with MET compared with SET in the autologous oocyte cycles (64.7% vs 53.2%, relative risk [RR] 1.24, 95% CI, 1.20-1.28), the multiple pregnancy rate was markedly greater (46.2% vs 1.4%, RR 32.56, 95% CI, 26.55-39.92). Donor oocyte cycles showed similar trends with an increased live-birth rate (62.0% vs 49.7%, RR 1.26, 95% CI, 1.11-1.46) and multiple pregnancy rate (54.0% vs 0.8%) seen with MET compared with SET. Preterm delivery rates and rates of low birth weight were significantly higher in MET compared with SET in both autologous and donor oocyte cycles and were also higher in the subanalysis of singleton deliveries that resulted from MET compared with SET. CONCLUSION: Despite some improvement in live-birth rate, nearly half of the pregnancies that resulted from MET of embryos that underwent PGT-A were multiples. Compared with SET, MET is associated with significantly higher rates of neonatal morbidity, including preterm delivery and low birth weight. The transfer of more than one embryo that underwent PGT-A should continue to be strongly discouraged, and patients should be counseled on the significant potential for adverse outcomes.

Psychological experience and coping strategies of patients in the Northeast US delaying care for infertility during the COVID-19 pandemic.

BACKGROUND: On March 17, 2020 an expert ASRM task force recommended the temporary suspension of new, non-urgent fertility treatments during an ongoing world-wide pandemic of Covid-19. We surveyed at the time of resumption of fertility care the psychological experience and coping strategies of patients pausing their care due to Covid-19 and examined which factors were associated and predictive of resilience, anxiety, stress and hopefulness. METHODS: Cross sectional cohort patient survey using an anonymous, self-reported, single time, web-based, HIPPA compliant platform (REDCap). Survey sampled two Northeast academic fertility practices (Yale Medicine Fertility Center in CT and Montefiore's Institute for Reproductive Medicine and Health in NY). Data from multiple choice and open response questions collected demographic, reproductive history, experience and attitudes about Covid-19, prior infertility treatment, sense of hopefulness and stress, coping strategies for mitigating stress and two validated psychological surveys to assess anxiety (six-item short-form State Trait Anxiety Inventory (STAl-6)) and resilience (10-item Connor-Davidson Resilience Scale, (CD-RISC-10). RESULTS: Seven hundred thirty-four patients were sent invitations to participate. Two hundred fourteen of 734 (29.2%) completed the survey. Patients reported their fertility journey had been delayed a mean of 10 weeks while 60% had been actively trying to conceive > 1.5 years. The top 5 ranked coping skills from a choice of 19 were establishing a daily routine, going outside regularly, exercising, maintaining social connection via phone, social media or Zoom and continuing to work. Having a history of anxiety (p < 0.0001) and having received oral medication as prior infertility treatment (p < 0.0001) were associated with lower resilience. Increased hopefulness about having a child at the time of completing the survey (p < 0.0001) and higher resilience scores (p < 0.0001) were associated with decreased anxiety. Higher reported stress scores (p < 0.0001) were associated with increased anxiety. Multiple multivariate regression showed being non-Hispanic black (p = 0.035) to be predictive of more resilience while variables predictive of less resilience were being a full-time homemaker (p = 0.03), having received oral medication as prior infertility treatment (p = 0.003) and having higher scores on the STAI-6 (< 0.0001). CONCLUSIONS: Prior to and in anticipation of further pauses in treatment the clinical staff should consider pretreatment screening for psychological distress and provide referral sources. In addition, utilization of a patient centered approach to care should be employed.

Fertility preservation for cancer patients: treatment gaps and considerations in patients' choices.

PURPOSE: Women with cancer may desire fertility preservation (FP) prior to initiating cancer treatment, but undergoing FP may result in treatment delays. This study sought to determine whether such delays existed in our population and which factors were associated with patients' decision to proceed with FP. METHODS: This was a historical cohort study performed at Montefiore Medical Center's Institute for Reproductive Medicine and Health. Reproductive age women diagnosed with cancer and consulted for FP were included. The main outcome measure was the number of days between FP consultation and cancer treatment initiation. Factors associated with patients' decisions to proceed with FP were also analyzed. RESULTS: Thirty out of 51 women in our study underwent FP including embryo cryopreservation, oocyte cryopreservation, ovarian tissue cryopreservation (OTC), both oocyte and embryo cryopreservation, or GnRH agonist treatment. The majority of women who underwent FP chose embryo cryopreservation (36.7%), followed by oocyte cryopreservation (33.3%). Of the 20 patients with partners who underwent FP, 13 (65%) froze embryos. Only 4 of the 30 women who underwent FP had all, or a portion of their services, covered by insurance. The mean treatment delay was 18 days (p = 0.007), with a mean consultation to oncologic treatment gap of 23 ± 16.8 and 41.4 ± 25.9 days in the non-FP and FP groups, respectively. CONCLUSION: Women with cancer diagnosis who underwent FP prior to initiating cancer treatment experienced a statistically significant delay in initiating cancer treatment. However, the clinical significance of this finding is unknown since FP treatments have not been associated with increased recurrence or mortality.

Status of nucleolar channel systems in uterine secretions accurately reflects their prevalence-a marker for the window of implantation-in simultaneously obtained endometrial biopsies.

OBJECTIVE: To assess whether nucleolar channel systems (NCSs) can be detected in exfoliated endometrial epithelial cells (EECs) of uterine secretions and whether such noninvasively determined NCS status is associated with significant NCS prevalence in simultaneously obtained endometrial biopsies. DESIGN: Prospective study (December 2015-February 2017). SETTING: University-affiliated and private fertility clinics. PATIENT(S): Luteal-phase patients of reproductive age requiring endometrial biopsy for medical indications. INTERVENTION(S): Uterine secretion aspiration before endometrial biopsy. Cells in uterine secretions were spun onto slides and fixed. NCSs were identified and quantified in cells and paraffin-embedded tissue sections by indirect immunofluorescence. MAIN OUTCOME MEASURE(S): Comparison of NCS status of uterine secretions with NCS prevalence in biopsies. Based on NCS detection, uterine secretions were assigned a status of NCS-positive (n = 15) or NCS-negative (n = 7). NCS prevalence in biopsies was expressed as a percentage of NCSs per EECs. RESULT(S): NCSs can be detected in exfoliated EECs of uterine secretions. Median NCS prevalence in endometrial biopsies from patients with NCS-positive secretions was 41.9% (interquartile range [IQR], 21.1-53.9) versus 2.0% (IQR, 0-6.9) when secretions were NCS-negative. The NCS status of secretions identified a significant difference in NCS prevalence of simultaneously obtained biopsies. CONCLUSION(S): NCS status of secretions accurately reflects NCS prevalence of biopsies, a marker for the implantation window. As secretion aspiration is compatible with same-day ET, our study provides proof of principle for a minimally invasive approach to determine endometrial receptivity for timing frozen ET.

Elevated Prevalence of Polycystic Ovary Syndrome and Cardiometabolic Disease in South Asian Infertility Patients.

South Asians (SA) develop cardiometabolic disease at elevated rates. We investigate whether reproductive-aged SA women are at higher risk for a precursor condition, polycystic ovary syndrome (PCOS), as compared to Caucasian controls. 52 SA and 52 Caucasian infertility patients from a single institution were included in a cross-sectional analysis. Outcomes were compared using Student's t, Mann-Whitney U, Pearson's Chi-squared and Fisher's exact tests. SA women were younger, with six-fold greater odds of PCOS. SA women were not obese, with similar body mass indices to controls. However, when screened, they demonstrated abundant metabolic disease, including insulin resistance, diabetes and dyslipidemia, and endometrial disease, including hyperplasia and polyps. The SA population was younger with more PCOS and high rates of metabolic and endometrial pathology. These findings, in the context of ethnicity-specific elevations in cardiometabolic risk, highlight the need for comprehensive screening and counseling in this patient population.

Male adiposity impairs clinical pregnancy rate by in vitro fertilization without affecting day 3 embryo quality.

OBJECTIVE: Male adiposity is detrimental for achieving clinical pregnancy rate (CPR) following assisted reproductive technologies (ART). The hypothesis that the association of male adiposity with decreased success following ART is mediated by worse embryo quality was tested. DESIGN AND METHODS: Retrospective study including 344 infertile couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles was performed. Cycle determinants included number of oocytes retrieved, zygote PN-score, total number of embryos available on day 3, number of embryos transferred, composite day 3 grade for transferred embryos, composite day 3 grade per cycle, and CPR. RESULTS: Couples with male body mass index (BMI) over 25 kg m(-2) (overweight and obese) exhibited significantly lower CPR compared to their normal weight counterparts (46.7% vs. 32.0% respectively, P = 0.02). No significant difference was observed for any embryo quality metrics when analyzed by male BMI: mean zygote PN-scores, mean composite day 3 grades for transferred embryos or composite day 3 grades per cycle. In a multivariable logistic regression analysis adjusting for female age, female BMI, number of embryos transferred and sperm concentration, male BMI over 25 kg m(-2) was associated with a lower chance for CPR after IVF (OR = 0.17 [95% CI: 0.04-0.65]; P = 0.01) but not after ICSI cycles (OR = 0.88 [95% CI: 0.41-1.88]; P = 0.75). In this cohort, male adiposity was associated with decreased CPR following IVF but embryo quality was not affected. CONCLUSIONS: Embryo grading based on conventional morphologic criteria does not explain the poorer clinical pregnancy outcomes seen in couples with overweight or obese male partner.

Full-sibling embryos created by anonymous gamete donation in unrelated recipients.

OBJECTIVE: To report the rare occurrence of full-sibling embryos in unrelated women using independently chosen donor sperm and donor oocytes in two different cycles unintentionally created at our IVF program, and to discuss the concept of disclosure to the patients. DESIGN: Case report. SETTING: Academic IVF program. PATIENT(S): Two women independently undergoing donor recipient cycles with anonymous donor oocytes and donor sperm. INTERVENTION(S): Both women received oocytes from the same donor several months apart and then by coincidence selected the same anonymous sperm donor to create anonymous full-sibling embryos. MAIN OUTCOME MEASURE(S): Clinical pregnancy after donor-recipient IVF cycle. RESULT(S): Both women conceived using the same donor sperm and donor oocytes in independent cycles, resulting in simultaneous pregnancy of full siblings. CONCLUSION(S): As providers with the knowledge that anonymous full sibling embryos have been created, we may have an obligation to disclose this information to the patients.

How many eggs are needed to produce an assisted reproductive technology baby: is more always better?

OBJECTIVE: To evaluate the association between the number of mature (metaphase II [MII]) oocytes per assisted reproductive technology (ART) cycle and the likelihood of live birth. DESIGN: Retrospective study. SETTING: Academic infertility practice. PATIENT(S): Seven hundred thirty-seven infertile women undergoing their initial fresh embryo, nondonor IVF or intracytoplasmic sperm injection cycle at Montefiore's Institute for Reproductive Medicine and Health between January 2002 and December 2008. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth. RESULT(S): Two hundred twenty-four cycles resulted in a live birth (30.4%). Live birth cycles had significantly more MII oocytes obtained per cycle as compared with their unsuccessful counterparts (11.0 ± 5.9 vs. 9.7 ± 6.2, respectively). Multivariate logistic regression was done to determine the minimum number of MII oocytes per cycle as a predictor of live birth after adjustment for age and historical maximum FSH values. Cycles that included the average number of MII in this cohort were used as a reference group. For cycles with five or fewer MII oocytes obtained, there was a statistically significant decrease in the likelihood of a live birth as compared with the reference group (odds ratio 0.61, 95% confidence interval 0.38-0.99). However, cycles with six or fewer obtained MII oocytes were not less likely to result in a live birth when compared with the reference group (odds ratio 0.69, 95% confidence interval 0.45-1.08). CONCLUSION(S): In our cohort, there was an advantage to obtaining six or more MII oocytes during the fresh oocyte retrieval compared with five or fewer oocytes. There was not an advantage, however, to obtaining 10 or more or 15 or more oocytes as compared with obtaining 6-9 oocytes. The strategy of aiming for a greater number of oocytes in an ART cycle should be revisited.

Prolonged gonadotropin stimulation is associated with decreased ART success.

PURPOSE: to evaluate whether the duration of gonadotropin stimulation predicts the likelihood of live birth after ART. METHODS: all IVF or ICSI cycles using fresh autologous oocytes at our institution between January 2004 and December 2007 were analyzed. RESULTS: out of 699 cycles resulting in oocyte retrieval, 193 produced a live birth (27.6%). Women who achieved a live birth had a significantly shorter stimulation phase (11.1 vs. 11.5 days, respectively). Multivariable analysis suggested that 13 days or longer of stimulation decreased the likelihood of a live birth by 53% as compared to cycles that were 10-12 days long (odds ratio [OR] 0.47; 95% confidence interval [CI]: 0.30-0.75) after adjustment for female age, maximum historical FSH, total dose of gonadotropin received, oocytes retrieved, embryos transferred, antagonist suppression and PCOS diagnosis. CONCLUSIONS: prolonged duration of gonadotropin stimulation is an independent negative predictor of ART success in our cohort.

Overweight men: clinical pregnancy after ART is decreased in IVF but not in ICSI cycles.

PURPOSE: To evaluate if elevated male body mass influences success after assisted reproductive technologies METHODS: Retrospective study of 290 cycles. RESULTS: Male body mass index greater than 25.0 kg/m² was associated with significantly lower clinical pregnancy (53.2% vs. 33.6%). Multivariable logistic regression indicated that the likelihood of clinical pregnancy was decreased if the male partner was overweight after in vitro fertilization but not after intracytoplasmic sperm injection (odds ratios: 0.21 [0.07-0.69] vs. 0.75 [0.38-1.49], respectively) after adjustment for number of embryos transferred, sperm concentration, female age and body mass. CONCLUSION: In this cohort, overweight status of the male partner was independently associated with decreased likelihood of clinical pregnancy after in vitro fertilization but not after intracytoplasmic sperm injection. A detrimental impact of higher male body mass was observed after adjusting for sperm concentration, suggesting that intracytoplasmic sperm injection may overcome some obesity related impairment of sperm-egg interaction.

A multidisciplinary approach to fertility-sparing therapy for a rare vulvar tumor.

OBJECTIVE: Case report of a young woman with a rare vulvar malignancy who received treatment with a personalized multidisciplinary approach to balance management of her malignancy without compromising survival with her desire for future pregnancy. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 33-year-old woman, gravida 2, para 1-0-1-1, who had a diagnosis of synovial cell sarcoma of the vulva and who desired future fertility. INTERVENTION(S): At multiple steps, treatment was planned to try to maximize fertility preservation without potentially affecting initial treatment, which included a radical hemivulvectomy with bilateral lymph node dissection, brachytherapy with interstitial needles (20 Gy), and external beam radiation therapy (50 Gy). MAIN OUTCOME MEASURE(S): Treatment and eradication of the malignancy and achievement of a successful subsequent pregnancy and live birth. RESULT(S): The patient had no evidence of disease for 2 years after treatment. During that time she received preconception counseling by both a perinatologist and a reproductive endocrinologist. She conceived with the use of ultrasound monitoring to time intercourse specifically with ovulation from the contralateral ovary and had an uncomplicated pregnancy with a term delivery. CONCLUSION(S): By using several disciplines and subspecialists, this patient received personalized treatment for a rare cancer, focused at curing her cancer and optimizing her future fertility.

Egg freezing, procreative liberty, and ICSI: the double standards confronting elective self-donation of oocytes.

The consensus view among relevant professional societies opposing the offering of elective oocyte cryopreservation for potential future self-donation withstands neither clinical nor ethical scrutiny. The favorable risk-benefit ratio of this technology mandates both the prioritization of patient autonomy for informed women seeking to maximize-not guarantee-their chances of having genetically related children, and a justification for viewing egg freezing differently from intracytoplasmic sperm injection.

Serum progesterone on the day of human chorionic gonadotropin administration predicts clinical pregnancy of sibling frozen embryos.

OBJECTIVE: To evaluate patient characteristics and fresh in vitro fertilization (IVF) cycle parameters that influence success of sibling frozen-thawed embryo transfer (FET) cycles. DESIGN: Retrospective study. SETTING: Academic infertility practice. PATIENT(S): Infertile women undergoing FET cycles using embryos cryopreserved on day 3 after insemination after an initial fresh IVF cycle. INTERVENTION(S): 90 FET cycles. MAIN OUTCOME MEASURE(S): Clinical pregnancy (CP). RESULT(S): The likelihood of CP after FET was statistically significantly higher in women who had achieved CP in the preceding fresh IVF cycle (71.4% vs. 40.6%). Multivariable logistic regression analysis confirmed that patients achieving CP after the fresh IVF cycle were more likely to achieve CP after FET (OR 5.5; 95% CI, 1.2-25.3) after adjusting for age, number, and cleavage status of embryos transferred. Additionally, higher serum levels of progesterone on the day of human chorionic gonadotropin administration emerged as predictive of CP after FET at a statistically significant level. CONCLUSION(S): The outcome of the fresh embryo transfer cycle is the foremost predictor of CP after FET of the sibling embryos. The relationship between serum progesterone on the day of human chorionic gonadotropin administration in the fresh cycle and the outcome of subsequent FET is noteworthy and merits further investigation.