Faculty Bibliography

BACKGROUND: Progesterone (P4) is essential for support of the endometrium and implantation of an embryo in the normal menstrual cycle. In programed frozen embryo transfer cycles using exogenous P4 is necessary, as the endogenous production of P4 requires a functioning corpus luteum that is not present in programed cycles. To date, there is continuing debate about ideal serum estradiol and P4 values in frozen embryo transfer cycles. METHODS: Patients underwent single euploid embryo frozen transfer cycles from 2010 to 2013 at a single large academic center. Patients using donor oocytes and patients with changes in progesterone dose during the cycles in question were excluded. All cycles were programed and intramuscular P4 was used exclusively. Only patients administering the same daily dose of P4 throughout the cycle were included (N = 213 patients). Main outcomes were ongoing pregnancy/live birth rates (OPR/LBR), clinical pregnancy rates (CPR), and spontaneous abortions/biochemical pregnancies. CPR was defined by the presence of a sac on 1st trimester ultrasound. Missed abortions were calculated per pregnancy with a sac. Receiver operator characteristic curves (ROC curves) and chi-squared tests were performed for statistical analysis. RESULTS: Two groups based on day 19 P4 levels were compared (group A, P4 < 20 ng/ml; group B, P4 > 20 ng/ml). OPR/LBRs were 65 vs. 49 %, group A vs. B, p value = 0.02, RR = 1.33 (1.1-1.7). Missed abortion and biochemical rates were higher in group B as opposed to group A, 27 vs. 12 %, p = 0.01, RR = 0.45(0.24-0.86). When P4 was stratified into five groups based on nanogram per milliliter of progesterone on day 19 (10-15, 15-20, 20-30, 30-40, and >40), there was a trend downward in OPR/LBR (70, 62, 52, 50, and 33 %, respectively). There was also an increase in missed abortion/biochemical rates (7, 15, 27, 32, and 20 %, respectively). Multiple logistic regression showed an increase in OPR/LBR when accounting for age, day 2 FSH, weight, number of embryos biopsied, and number of euploid embryos. CONCLUSION: P4 levels >20 ng/ml on the day of transfer (during frozen single euploid embryo transfer cycles) were associated with decreased OPR/LBR.

This longitudinal study reports preliminary findings of six patients who underwent first polar body biopsy followed by oocyte vitrification. All oocytes were warmed, inseminated by intracytoplasmic sperm injection and cultured to blastocyst. All suitable blastocysts underwent trophectoderm biopsy for aneuploidy screening, and supernumerary blastocysts were vitrified. Euploid blastocysts were transferred either fresh or in a subsequent programmed cycle. Of the 91 metaphase II oocytes, 30 had euploid first polar bodies. Development to blastocyst was more likely in oocytes with a euploid first polar body (66.7% versus 24.6%; P < 0.001). Nineteen euploid blastocysts were produced: 10 from oocytes with a euploid first polar body and nine from oocytes with an aneuploid first polar body. Five out of six patients (83%) had a live birth or ongoing pregnancy at the time of analysis. Eleven euploid blastocysts have been transferred and seven implanted (64%). Although the chromosomal status of the first polar body was poorly predictive of embryonic ploidy, an association was found between chromosomal status of the first polar body and development to blastocyst. Further study is required to characterize these relationships, but proof of concept is provided that twice biopsied, twice cryopreserved oocytes and embryos can lead to viable pregnancies.

BACKGROUND: Low functional ovarian reserve (LFOR) has been associated with hypoandrogenemia and increased embryo aneuploidy, while androgen supplementation has been reported to improve aneuploidy rates. We, therefore, assessed whether in infertile women undergoing in vitro fertilization (IVF) androgen concentrations are associated with aneuploidy rates. METHODS: This study was performed in 2 academically affiliated fertility centers in New York City and an academically affiliated steroid chemistry laboratory in Utah. Androgen concentrations were measured in blinded fashion from 84 infertile women (age 40.3 +/- 2.4 years) at New York University (NYU), using a validated LC-MS/MS method, in cryopreserved serum samples of patients who had undergone IVF with concomitant preimplantation genetic screening (PGS), utilizing a 24-chromosome platform. The Center for Human Reproduction (CHR) provided plasma samples of 100 historical controls (ages 38.6+/-5.0 years) undergoing IVF without PGS. Statistical comparisons were made of androgen concentrations, and of associations between androgen concentrations and embryo aneuploidy. RESULTS: Women undergoing IVF + PGS at NYU revealed no association between embryo aneuploidy and androgen concentrations but demonstrated significantly lower androgen concentrations than the 100 control patients from CHR, CONCLUSIONS: Though this study revealed no association between androgen levels and embryo ploidy, the extremely low androgen levels in the NYU study group raise the possibility of a threshold effect below which testosterone no longer affects aneuploidy. Before an androgen effect on embryo ploidy can be completely ruled out, a patient population with more normal androgen levels has to be investigated.