K.N. Goldman

Baby budgeting: oocyte cryopreservation in women delaying reproduction can reduce cost per live birth.

OBJECTIVE To determine whether oocyte cryopreservation for deferred reproduction is cost effective per live birth using a model constructed from observed clinical practice. DESIGN Decision-tree mathematical model with sensitivity analyses. SETTING Not applicable. PATIENT(S) A simulated cohort of women wishing to delay childbearing until age 40 years. INTERVENTION(S) Not applicable. MAIN OUTCOME MEASURE(S) Cost per live birth. RESULT(S) Our primary model predicted that oocyte cryopreservation at age 35 years by women planning to defer pregnancy attempts until age 40 years would decrease cost per live birth from

Successful Oocyte Cryopreservation in Reproductive-Aged Cancer Survivors.

55,060 to

mTORC1/2 inhibition preserves ovarian function and fertility during genotoxic chemotherapy

39,946 (and increase the odds of live birth from 42% to 62% by the end of the model), indicating that oocyte cryopreservation is a cost-effective strategy relative to forgoing it. If fresh autologous assisted reproductive technology (ART) was added at age 40 years, before thawing oocytes, 74% obtained a live birth, and cost per live birth increased to

Association of body mass index with embryonic aneuploidy

61,887. Separate sensitivity analyses demonstrated that oocyte cryopreservation remained cost effective as long as performed before age 38 years, and more than 49% of those women not obtaining a spontaneously conceived live birth returned to thaw oocytes. CONCLUSION(S) In women who plan to delay childbearing until age 40 years, oocyte cryopreservation before 38 years of age reduces the cost to obtain a live birth.

Pregnancy Outcomes After Fertility Preservation in Transgender Men

OBJECTIVE: To demonstrate that oocyte cryopreservation is a feasible reproductive option for patients with cancer of childbearing age who require gonadotoxic therapies. METHODS: This study is a university-based retrospective review of reproductive-aged cancer patient treatment cycles that included ovarian stimulation, transvaginal oocyte retrieval, oocyte cryopreservation, and, in some cases, subsequent oocyte thaw, in vitro fertilization, and embryo transfer. Outcome measures included ovarian stimulation response, number of oocytes retrieved, cryopreserved, and thawed, and pregnancy data. RESULTS: From 2005 to 2014, 176 reproductive-aged patients with cancer (median age 31 years, interquartile range 24–36) completed 182 oocyte cryopreservation cycles. Median time between consult request and oocyte retrieval was 12 days (interquartile range 10–14). Median peak stimulation estradiol was 1,446 pg/mL (interquartile range 730–2,687); 15 (interquartile range 9–23) oocytes were retrieved and 10 (interquartile range 5–18) metaphase II oocytes were cryopreserved per cycle. Ten patients (11 cycles) have returned to attempt pregnancy with their cryopreserved oocytes. Among thawed oocytes, the cryopreservation survival rate was 86% (confidence interval [CI] 78–94%). Nine of 11 thaw cycles resulted in embryos suitable for transfer. The embryo implantation rate was 27% (CI 8–46%) and the live birth rate was 44% (CI 12–77%) per embryo transfer. Chance for live birth with embryos created from cryopreserved oocytes was similar between the patients with cancer in this study and noncancer patients who underwent the same treatment at our center (44% [CI 12–77%] compared with 33% [CI 22–44%] per embryo transfer). CONCLUSION: Oocyte cryopreservation is now a feasible fertility preservation option for reproductive-aged patients with cancer who require gonadotoxic therapies.

Interactive case-based learning improves resident knowledge and confidence in reproductive endocrinology and infertility*

Significance A major unresolved issue for premenopausal women undergoing chemotherapy is infertility due to the loss of nonrenewable ovarian primordial follicles. We show that pharmacologic down-regulation of the mammalian/mechanistic target of rapamycin (mTOR) pathway during chemotherapy in a mouse model prevents activation of primordial follicles, preserves ovarian function, and maintains normal fertility using clinically available inhibitors of mTOR complex (C)1 and mTORC1/2. These findings represent a feasible pharmacologic approach for preservation of ovarian function and fertility during treatment with conventional chemotherapy. The ovary contains oocytes within immature (primordial) follicles that are fixed in number at birth. Activation of follicles within this fixed pool causes an irreversible decline in reproductive capacity, known as the ovarian reserve, until menopause. Premenopausal women undergoing commonly used genotoxic (DNA-damaging) chemotherapy experience an accelerated loss of the ovarian reserve, leading to subfertility and infertility. Therefore, there is considerable interest but little effective progress in preserving ovarian function during chemotherapy. Here we show that blocking the kinase mammalian/mechanistic target of rapamycin (mTOR) with clinically available small-molecule inhibitors preserves ovarian function and fertility during chemotherapy. Using a clinically relevant mouse model of chemotherapy-induced gonadotoxicity by cyclophosphamide, and inhibition of mTOR complex 1 (mTORC1) with the clinically approved drug everolimus (RAD001) or inhibition of mTORC1/2 with the experimental drug INK128, we show that mTOR inhibition preserves the ovarian reserve, primordial follicle counts, serum anti-Mullerian hormone levels (a rigorous measure of the ovarian reserve), and fertility. Chemotherapy-treated animals had significantly fewer offspring compared with all other treatment groups, whereas cotreatment with mTOR inhibitors preserved normal fertility. Inhibition of mTORC1 or mTORC1/2 within ovaries was achieved during chemotherapy cotreatment, concomitant with preservation of primordial follicle counts. Importantly, our findings indicate that as little as a two- to fourfold reduction in mTOR activity preserves ovarian function and normal birth numbers. As everolimus is approved for tamoxifen-resistant or relapsing estrogen receptor-positive breast cancer, these findings represent a potentially effective and readily accessible pharmacologic approach to fertility preservation during conventional chemotherapy.

2017 in-training initiative of the Journal of Assisted Reproduction and Genetics : the JARG Young Investigator Forum

OBJECTIVE To determine whether an association exists between body mass index (BMI) and embryo ploidy in patients undergoing in vitro fertilization (IVF) with trophectoderm biopsy and 24-chromosome preimplantation genetic screening (PGS). DESIGN Retrospective cohort study. SETTING University-based fertility center. PATIENT(S) 279 women aged 20-45 years with documented height and weight from the day of oocyte retrieval who underwent 24-chromosome PGS between 2010 and 2013. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) PRIMARY OUTCOMES number and percentage of euploid embryos. RESULT(S) Patients were grouped by World Health Organization (WHO) BMI class: underweight (<18.5, n = 11), normal weight (18.5-24.9, n = 196), overweight (25-29.9, n = 50), and obese (≥30, n = 22). Groups were similar by age (mean ± standard error of the mean: 37.5 ± 1.2 to 39.2 ± 0.9), ovarian reserve, and IVF cycle parameters. There was no difference in the number or percentage of euploid embryos by BMI category (<18.5: 27.6% ± 8.5; 18.5-24.9: 34.5% ± 2.2; 25-29.9: 32.1% ± 4.3; ≥30: 30.9% ± 7.3). Age was inversely related to euploidy, but adjusted multivariate regression models failed to demonstrate a statistically significant relationship between BMI and euploidy in underweight (adjusted odds ratio [AOR] 0.44; 95% confidence interval [CI], 0.09-2.10), overweight (AOR 0.90; 95% CI, 0.43-2.00), or obese (AOR 0.74; 95% CI, 0.25-2.20) patients compared with the normal-weight reference group. CONCLUSION(S) No statistically significant relationship was identified between BMI and euploidy in an otherwise homogenous cohort of patients undergoing IVF with PGS, suggesting that the negative impact of overweight and obesity on IVF and reproductive outcomes may not be related to aneuploidy.

Oocyte efficiency: does live birth rate differ when analyzing cryopreserved and fresh oocytes on a per-oocyte basis?

BACKGROUND Transgender individuals, individuals whose gender identity does not align with their sex assigned at birth, undergoing gender-affirming hormonal or surgical therapies may experience loss of fertility. Assisted reproductive technologies have expanded family-building options for transgender men who were assigned female at birth. CASES Three transgender men underwent oocyte cryopreservation before gender-affirming hormonal therapy. One patient underwent fertility preservation as an adolescent. Two adult patients had children using their cryopreserved oocytes, with the pregnancies carried by their sexually intimate partners. CONCLUSION Transgender men with cryopreserved gametes can build families in a way that affirms their gender identity. Obstetrician-gynecologists should be familiar with the fertility needs of transgender patients so appropriate discussions and referrals can be made.

Long-term cryopreservation of human oocytes does not increase embryonic aneuploidy

Abstract Resident physicians’ scores on the REI section of the CREOG exam are traditionally low, and nearly 40% of house staff nation-wide perceive their REI knowledge to be poor. We aimed to assess whether an interactive case-based group-learning curriculum would narrow the REI knowledge gap by improving understanding and retention of core REI concepts under the time constraints affecting residents. A three-hour case-based workshop was developed to address four primary CREOG objectives. A multiple-choice test was administered immediately before and after the intervention and 7 weeks post-workshop, to evaluate both knowledge and confidence. Following the intervention, residents self-reported increased confidence with counseling and treatment of PCOS, ovulation induction cycle monitoring, counseling and treatment of POI, and breaking bad news related to infertility (p < 0.05). The multiple-choice exam was re-administered 7 weeks post-intervention, and scores remained significantly improved compared to pre-workshop scores (p < 0.05). At that time, all residents either strongly agreed (91.7%) or agreed (8.3%) that the case-based interactive format was preferable to traditional lecture-based teaching. In conclusion, a nontraditional curriculum aimed at teaching core REI concepts to residents through interactive case-based learning can be successfully integrated into a residency curriculum, and significantly improves knowledge and confidence of critical concepts in REI.

Preimplantation Genetic Diagnosis (PGD) for Monogenic Disorders: the Value of Concurrent Aneuploidy Screening

The Journal of Assisted Reproduction and Genetics introduces the JARG Young Investigator Forum, an in-training initiative aimed to expand opportunities for young investigators. The JARG Young Investigator Forum has three primary goals: first, to increase opportunities for trainees and young investigators to contribute as researchers and writers. Trainees will be invited to publish mini-reviews based on their area of research interest/expertise and will have the opportunity to indicate “in-training” when submitting manuscripts as first author Educational research pertaining to reproductive medicine training will be added to the purview of the journal. Second, the Young Investigator Forum will increase opportunities for trainees to serve as journal reviewers and will provide mentorship throughout the peer review process. Third, trainees will have the unique opportunity to gain editorial experience by serving as a “guest editor” of the Young Investigator Forum, overseeing all editorial aspects of their assigned particular issue. Through authorship, peer review, and editorial experience, we seek to nurture the academic skills that are critical to a well-rounded career. The JARG Young Investigator Forum aims to foster career development for a generation of trainees who represent the future of reproductive medicine, and here, we outline the primary goals and objectives of the initiative.