Estradiol to progesterone ratio is not a predictor of oocyte maturity at time of ovulation trigger.

PURPOSE: To evaluate the relationship between progesterone and oocyte maturity rate via estradiol to progesterone ratio (E/P) at the time of ovulatory trigger. METHODS: This is a retrospective cohort study of first autologous IVF cycles from January to December 2018 from a private practice fertility center. Serum estradiol and progesterone levels were measured on the day of ovulatory trigger. E/P was calculated to control for degree of response. Embryos were cultured to the blastocyst stage for trophectoderm biopsy. Preimplantation genetic testing for aneuploidy (PGT-A) was performed using next-generation sequencing (NGS). Oocyte retrieval rate (oocytes retrieved/follicles ≥ 13 mm), maturity rate (MII/oocytes retrieved), and euploid rate (euploid/total biopsied embryos) were calculated. Clinical pregnancy, ongoing pregnancy (> 10 weeks), and live births following frozen embryo transfer (FET) were examined in relation to E/P. Regression analyses were performed to analyze E/P as a categorical value (defined by quartile) on oocyte maturity. RESULTS: Two hundred eleven women underwent controlled ovarian hyperstimulation and had steroid levels at trigger available. Mean E at trigger was 3449 ± 2040 pg/mL while mean P was 1.13 ± 0.58 ng/mL, with mean E/P of 3.36 + 2.04. There were no differences between quartiles of E/P with respect to retrieval, maturity rate, or euploid rate. Two hundred eleven IVF cycles resulted in 138 euploid frozen embryo transfers. There were no differences between quartiles of E/P with respect to clinical pregnancy, ongoing pregnancy, or live birth rate. CONCLUSION: E/P ratio at the time of trigger does not impact oocyte retrieval rate, maturity rate, or euploid rate. Pregnancy and live birth outcomes were also not impacted.

Euploid rates among oocyte donors: is there an optimal age for donation?

PURPOSE: To examine cycle blastocyst euploid rates among age subgroups of oocyte donors. METHODS: Retrospective cohort analysis of ova donation in vitro fertilization cycles (OD-IVF) for which trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A) by array comparative genomic hybridization (aCGH) or next generation gene sequencing (NGS) was employed between January 2015 and December 2018 in a single high-volume fertility center. RESULTS: Compared to oocyte donors age 26-30, oocyte donors age ≤ 25 had similar cycle blastocyst euploid rates (80 [66.7, 87.5]%, vs. 75 [62.5, 87.5]%, median [IQR], p = 0.07), blastocyst formation rates (66.7 [50, 75]%, vs. 62.5 [52, 75]%, p = 0.55), and number of retrieved oocytes (29 [23, 37] vs. 27 [20, 35], p = 0.18). Age of oocyte donor from 18 to 34 was not correlated with cycle blastocyst euploid rate. CONCLUSION: Oocyte donors age ≤ 25 had similar cycle blastocyst euploid rates, blastocyst formation rates, and number of retrieved oocytes compared to donors age 26-30. There was no correlation between cycle blastocyst euploid rates and age of the oocyte donor from 18 to 34 years. Given the lack of significant age-related change in cycle blastocyst euploid rates, our data support existing practices which do not favor a specific age subgroup of young oocyte donors.

Transfer of embryos with segmental mosaicism is associated with a significant reduction in live-birth rate.

OBJECTIVE: To evaluate the impact of segmental mosaicism on pregnancy outcomes from the transfer of embryos previously designated as euploid. DESIGN: Retrospective cohort analysis. SETTING: Single, private, high-volume fertility center. PATIENT(S): Three hundred and twenty-seven women who underwent 377 frozen single euploid embryo transfers. INTERVENTION(S): Trophectoderm biopsy of embryos cultured to the blastocyst stage, where all transferred embryos were designated euploid by high-density oligonucleotide array comparative genomic hybridization (aCGH); after ascertaining all outcomes, revaluation of aCGH results for evidence of segmental mosaicism (defined as mosaicism on a portion of a chromosome). MAIN OUTCOME MEASURE(S): Live-birth rate and spontaneous abortion rate. RESULT(S): Of the 377 embryos transferred, 357 were euploid with no mosaicism, and 20 embryos had segmental mosaicism. Segmental mosaics had a statistically significantly lower live-birth rate compared with euploid controls (30.0% vs. 53.8%). When controlling for age and day of Trophectoderm biopsy, the odds for live birth after transfer of segmental mosaics were reduced by 66% compared with euploid controls (0.34; 95% confidence interval, 0.13-0.92). The spontaneous abortion rate was statistically significantly higher after transfer of segmental mosaics compared with euploid controls (40.0% vs. 18.2%). CONCLUSION(S): Blastocysts with segmental mosaicism have reduced reproductive potential but retain the ability to result in live birth. These results support reporting segmental mosaicism to optimize selection of a single embryo for transfer that will maximize the chance of life birth.

Earlier day of blastocyst development is predictive of embryonic euploidy across all ages: essential data for physician decision-making and counseling patients.

PURPOSE: The purpose of this study is to evaluate whether day of blastocyst development is associated with embryo chromosomal status as determined by high-density oligonucleotide microarray comparative genomic hybridization (aCGH). METHODS: This is a retrospective cohort analysis, including women who underwent in vitro fertilization (IVF) with trophectoderm biopsy at a single private fertility center from January 2014 to December 2014. Repeat cycles were excluded. Cycles were assessed for percentage of blastocysts biopsied on days 5, 6, or 7 and rate of euploid embryos per cycle. Cycles were stratified by Society for Assisted Reproductive Technology (SART) age groups (< 35, 35-37, 38-40, 41-42, > 42) and by donor status. RESULTS: A total of 388 IVF cycles and 2132 biopsied blastocysts were evaluated. The percentages of blastocysts biopsied on days 5, 6, and 7 were 62.5, 35.8, and 1.7%, respectively. Blastocyst euploid rates on days 5, 6, and 7 were 49.5, 36.5, and 32.9%, respectively. Earlier blastocyst development was associated with a significantly increased euploid rate (p < 0.0001). Younger maternal age (p < 0.0001) and higher number of blastocysts biopsied per patient (p = 0.0063) were both independently associated with greater percentage of euploidy. CONCLUSIONS: Earlier blastocyst development is independently associated with a higher likelihood of embryonic euploidy in both autologous and donor embryos. In non-biopsied embryos, these data support selection of day 5 blastocysts for transfer over later-developing embryos. These results can assist with patient counseling regarding expectations and outcomes. To our knowledge, this is the first study to examine embryonic euploidy as stratified by both day of blastocyst development and SART age group.

A randomized, controlled trial comparing the efficacy and safety of aqueous subcutaneous progesterone with vaginal progesterone for luteal phase support of in vitro fertilization.

STUDY QUESTION: Is the ongoing pregnancy rate with a new aqueous formulation of subcutaneous progesterone (Prolutex(®)) non-inferior to vaginal progesterone (Endometrin(®)) when used for luteal phase support of in vitro fertilization? SUMMARY ANSWER: In the per-protocol (PP) population, the ongoing pregnancy rates per oocyte retrieval at 12 weeks of gestation were comparable between Prolutex and Endometrin (41.6 versus 44.4%), with a difference between groups of -2.8% (95% confidence interval (CI) -9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support. WHAT IS KNOWN ALREADY: Luteal phase support has been clearly demonstrated to improve pregnancy rates in women undergoing in vitro fertilization (IVF). Because of the increased risk of ovarian hyperstimulation syndrome associated with the use of hCG, progesterone has become the treatment of choice for luteal phase support. STUDY DESIGN, SIZE, DURATION: This prospective, open-label, randomized, controlled, parallel-group, multicentre, two-arm, non-inferiority study was performed at eight fertility clinics. A total of 800 women, aged 18-42 years, with a BMI of ≤ 30 kg/m(2), with <3 prior completed assisted reproductive technology (ART) cycles, exhibiting baseline (Days 2-3) FSH of ≤ 15 IU/L and undergoing IVF at 8 centres (seven private, one academic) in the USA, were enrolled from January 2009 through June 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 800 women undergoing IVF were randomized after retrieval of at least three oocytes to an aqueous preparation of progesterone administered subcutaneously (25 mg daily) or vaginal progesterone (100 mg bid daily). Randomization was performed to enrol 100 patients at each site using a randomization list that was generated with Statistical Analysis Software (SAS(®)). If a viable pregnancy occurred, progesterone treatment was continued up to 12 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE: Using a PP analysis, which included all patients who received an embryo transfer (Prolutex = 392; Endometrin = 390), the ongoing pregnancy rate per retrieval for subcutaneous versus vaginal progesterone was 41.6 versus 44.4%, with a difference between groups of -2.8% (95% CI -9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support. In addition, rates of initial positive ß-hCG (56.4% subcutaneous versus 59.0% vaginal; 95% CI -9.5, 4.3), clinical intrauterine pregnancy with fetal cardiac activity (42.6 versus 46.4%; 95% CI -10.8, 3.2), implantation defined as number of gestational sacs divided by number of embryos transferred (33.2 versus 35.1%; 95% CI -7.6, 4.0), live birth (41.1 versus 43.1%; 95% CI -8.9, 4.9) and take-home baby (41.1 versus 42.6%; 95% CI -8.4, 5.4) were comparable. Both formulations were well-tolerated, with no difference in serious adverse events. Analysis with the intention-to-treat population also demonstrated no difference for any outcomes between the treatment groups. LIMITATIONS, REASONS FOR CAUTION: The conclusions are limited to the progesterone dosing regimen studied and duration of treatment for the patient population examined in this study. WIDER IMPLICATIONS OF THE FINDINGS: Subcutaneous progesterone represents a novel option for luteal phase support in women undergoing IVF who for personal reasons prefer not to use a vaginal preparation or who wish to avoid the side effects of vaginal or i.m. routes of administration. STUDY FUNDING/COMPETING INTERESTS: The study was funded by Institut Biochimique SA (IBSA). CAJ, BC, ST and CJ are employees of IBSA. FH currently consults for IBSA. TRIAL REGISTRATION NUMBER: NCT00828191.