Faculty Bibliography

CONTEXT/BACKGROUND:Postpartum depression (PPD) is a serious psychiatric disorder. While causes remain poorly understood, perinatal sex hormone fluctuations are an important factor, and allopregnanolone in particular has emerged as a key determinant. While synthetic environmental chemicals such as bisphenols and phthalates are known to affect sex hormones, no studies have measured allopregnanolone and the consequences of these hormonal changes on PPD have not been interrogated. OBJECTIVE:To investigate associations of repeated measures of urinary bisphenols and phthalates in early- and mid-pregnancy with serum pregnenolone, progesterone, allopregnanolone, and pregnanolone concentrations in mid-pregnancy and PPD symptoms at four months postpartum. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION/UNASSIGNED:Prospective cohort study of 139 pregnant women recruited between 2016-18. Bisphenols and phthalates were measured in early- and mid-pregnancy urine samples. Serum sex steroid hormone concentrations were measured in mid-pregnancy. PPD was assessed at 4 months postpartum using the Edinburgh Postnatal Depression Scale (EPDS). Multiple informant models were fit using generalized estimating equations. MAIN OUTCOME MEASURES/METHODS:Serum levels of allopregnanolone, progesterone, pregnanolone, and pregnenolone were examined as log-transformed continuous variables. PPD symptoms were examined as continuous EPDS scores and dichotomously with scores ≥10 defined as PPD. RESULTS:Di-n-octyl phthalate (DnOP) and diisononyl phthalate (DiNP) metabolites were associated with reduced progesterone concentrations. Log-unit increases in ∑DnOP and ∑DiNP predicted 8.1% (95% Confidence Interval (CI): -15.2%, -0.4%) and 7.7% (95% CI: -13.3%, -1.7%) lower progesterone, respectively. ∑DnOP was associated with increased odds of PPD (odds ratio=1.48 (95% CI: 1.04, 2.11)). CONCLUSIONS:Endocrine disrupting chemicals may influence hormonal shifts during pregnancy as well as contribute to PPD.

PURPOSE/OBJECTIVE:In the era of personalized medicine and the increased use of frozen embryo transfer (FET), assay of the endometrium's receptivity prior to transfer has gained popularity, especially among patients. However, the optimal timing for single thawed euploid embryo transfers (STEET) in a programmed FET has yet to be determined Mackens et al. (Hum Reprod. 32(11):2234-42, 2017). We sought to examine the outcomes of euploid FETs by length of progesterone (P4) exposure. METHODS:Prospective cohort study of programmed FETs of single euploid embryos between June 1, 2018, and December, 18, 2018, at our center. Subjects reported the exact start time for initiating progesterone. The transfer time was noted to calculate the primary independent variable, duration of progesterone exposure. Statistical analysis included ANOVA and Spearman's rho correlation, with p < 0.05 considered significant. RESULTS:Inclusion criteria were met for 253 programmed STEET cycles in the analysis. There was no significant difference in P4 duration when comparing outcome groups (112.8 ± 3.1 ongoing pregnancy (OP), 112.4 ± 4.4 spontaneous abortion (SAB), 111.6 ± 1.7 biochemical pregnancy (BP), 113.9 ± 5.7 no pregnancy (NP), F 1.76, df 3, p = 0.16). An ROC curve assessing the ability of P4 duration to predict ongoing pregnancy (OP) had an area under the curve of 0.467 (p = 0.38). CONCLUSION/CONCLUSIONS:Duration of P4 was not associated with outcome. Of the cycles, 65.6% resulted in ongoing pregnancy with our center's instructions resulting in an average progesterone exposure of 112.8 h, with a range of 98.3-123.7 h. With growing popularity for individualized testing, these results provide evidence for patient counseling of the high likelihood of ongoing pregnancy without personalized testing.

PURPOSE/OBJECTIVE:To characterize the demographic differences between infertile/sub-fertile women who utilized infertility services vs. those that do not. METHODS:A retrospective analysis of cross-sectional data obtained during the 2011-2013, 2013-2015, and 2015-2017 cycles of National Survey for Family Growth from interviews administered in home for randomly selected participants by a National Center of Health Statistics (NCHS) surveyor was used to analyze married, divorced, or women with long-term partners who reported difficulty having biological children (sub-fertile/infertile women). Demographic differences such as formal marital status, education, race, and religion were compared between women who presented for infertility care vs. those that did not. The primary outcome measure was presenting for infertility evaluation and subsequently utilizing infertility services. Healthcare utilization trends such as having a usual place of care and insurance status were also included as exposures of interest in the analysis. RESULTS:Of the 12,456 women included in the analysis 1770 (15.3%) had used infertility services and 1011 (8.3%) said it would be difficult for them to have a child but had not accessed infertility services. On univariate analysis, compared to women who used infertility services, untreated women had lower average household incomes (295.3 vs. 229.8% of the federal poverty line respectively). Untreated women also had lower levels of education and were more likely to be divorced or never have married. In terms of health status, unevaluated women were less likely to have a usual place for healthcare (87.3%) as compared to women presenting for fertility care (91.9%) (p = 0.004). When examining insurance status, 23.3% of unevaluated women were uninsured as compared to 8.3% of evaluated women. On multivariate analysis, infertile women without insurance were at 0.37 odds of utilizing infertility care compared to women with insurance. CONCLUSIONS:Demographic factors are associated with the utilization of infertility care. Insurance status is a significant predictor of whether or not infertile women will access treatment. Data from the three most recent NSFG surveys along with prior analyses demonstrate the need for expanded insurance coverage in order to address the socioeconomic disparities between infertile women who are accessing services vs. those that are not.

OBJECTIVE:To evaluate the outcomes of planned oocyte cryopreservation patients most likely to have a final disposition. DESIGN/METHODS:Retrospective cohort study of all patients who underwent at least 1 cycle of planned oocyte cryopreservation between Jan 2005 and December 2009. SETTING/METHODS:Large urban University-affiliated fertility center PATIENT(S): All patients who underwent ≥1 cycle of planned oocyte cryopreservation in the study period. INTERVENTION(S)/METHODS:None MAIN OUTCOME MEASURE(S): Primary outcome was the disposition of oocytes at 10-15 years. Secondary outcomes included thaw/warming types, laboratory outcomes, and live birth rates. Outcomes and variables treated per patient. RESULT(S)/RESULTS:A total of 231 patients with 280 cycles were included. The mean age at the first retrieval was 38.2 years (range 23-45). A total of 3,250 oocytes were retrieved, with an average of 10 metaphase II frozen/retrieval. To date, the oocytes of 88 patients (38.1%) have been thawed/warmed, 109 (47.2%) remain in storage, 27 (11.7%) have been discarded, and 7 (3.0%) have been transported elsewhere. The return rate (patients who thawed/warmed oocytes) was similar by Society for Assisted Reproductive Technology age group. The mean age of patients discarding oocytes was 47.4 years (range, 40-57). Of the 88 patients who thawed/warmed oocytes, the mean age at the time of thaw/warming was 43.9 years (range, 38-50) with a mean of 5.9 years frozen (range, 1-12). Nine patients (10.2%) thawed/warmed for secondary infertility. A total of 62.5% of patients created embryos with a partner, and 37.5% used donor sperm. On average, 14.3 oocytes were thawed/warmed per patient, with 74.2% survival (range, 0%-100%) and a mean fertilization rate of 68.8% of surviving oocytes. Of 88 patients, 39 (44.3%) planned a fresh embryo transfer (ET); 36 of 39 patients had at least 1 embryo for fresh ET, and 11 had a total of 14 infants. Forty-nine of 88 patients (55.7%) planned for preimplantation genetic testing for aneuploidy, with a mean of 4.2 embryos biopsied (range, 0-14) and a euploidy rate of 28.9%. Of the 49 patients, 17 (34.7%) had all aneuploidy or no embryos biopsied. Twenty-four patients underwent a total of 36 single euploid ET with 18 live births from 16 patients. Notably, 8 PGT-A patients had a euploid embryo but no ET, affecting the future cumulative pregnancy rate. Overall, 80 patients with thaw/warming embryos had a final outcome. Of these, 20 had nothing for ET (arrested/aneuploid), and of the 60 who had ≥1 ET, 27 had a total of 32 infants, with a live birth rate of 33.8% (27/80). CONCLUSION(S)/CONCLUSIONS:We report the final outcomes of patients most likely to have returned, which is useful for patient counseling: a utilization rate of 38.1% and a no-use rate of 58.9%, similar across age groups. Further studies with larger cohorts as well as epidemiologic comparisons to patients currently cryopreserving are needed.