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Purpose: The rate of embryonic aneuploidy increases with increasing female age and is the primary cause of lower pregnancy and live birth rates (LBR) in older reproductive age women. This retrospective cohort study evaluates single euploid embryo transfers to determine whether an age-related decline in reproductive efficiency persists. Methods: A total of 8175 non-donor single embryo transfers (SET) after pre-implantation testing for aneuploidy (PGT-A) and cryopreservation were included. These were divided into five groups by patient age: < 35 years old (n = 3789 embryos transferred), 35–37 (n = 2200), 38–40 (n = 1624), 41–42 (n = 319), and > 42 (n = 243). Implantation rate (IR), clinical pregnancy rate (CPR), and LBR were calculated for each group as a percentage of embryos transferred and compared. CPR was also analyzed as a percentage of implanted pregnancies, and LBR as a percentage of clinical pregnancies, to determine when age has the greatest impact. These results were then adjusted for confounding variables via a multivariate logistic regression model. Results: Implantation rates negatively correlated with age. After adjusting for confounders, women 38 years or older had a significantly lower IR than those under 35 (OR 0.85, 95%CI 0.73–0.99 for 38–40 years old; 0.69, 0.53–0.91 for 41–42, and 0.69, 0.51–0.94 for > 42). These differences are also apparent in CPR and LBR. The rates of progression to clinical pregnancy and live birth did not differ significantly by age group. Other factors observed to affect IR independently were anti-Müllerian hormone (AMH), day of embryo transfer, and embryo morphology. Conclusion: While selection of euploid embryos may be effective in overcoming a significant proportion of the age-related decline in reproductive efficiency, a decrease in IR, CPR, and LBR persists even when analyzing only euploid embryo transfers. The observed impact of aging is, therefore, independent of ploidy, as well as of other variables that affect reproductive efficiency. These results indicate that factors other than aneuploidy contribute to reproductive senescence. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate if sperm DNA fragmentation (SDF) in the sample used for intracytoplasmic sperm injection (ICSI) impacts outcomes after euploid blastocyst transfer. Methods: Prospective cohort study of couples undergoing IVF with preimplantation genetic testing for aneuploidy from December 2014–June 2017. Sperm collected on the day of ICSI was analyzed for SDF using the sperm chromatin structure assay (SCSA®). Semen analysis parameters, embryologic outcomes, and clinical outcomes after euploid blastocyst transfer were compared between groups with DNA fragmentation index (DFI) ≤ 15% and DFI > 15% using Mann–Whitney U, t tests, and generalized linear mixed effects models. Results: Two hundred thirty-four patients were included. One hundred seventy-nine men had DFI ≤ 15% (low DFI group) and 55 men had DFI > 15% group (high DFI group). Total motile sperm and sperm concentration were significantly lower in the group with DFI > 15% vs. DFI ≤ 15%. There was no difference in fertilization (86.3 vs. 84.2%, adjusted OR (95% CI) 0.86 (0.63–1.18)), blastulation (49.5 vs. 48.8%, adjusted OR 1.02 (0.75–1.36)), or euploidy (55.7 vs. 52.1%, adjusted OR 0.96 (0.7–1.31)) between the low and high DFI groups, respectively. Clinical outcomes were similar between low and high DFI groups, including implantation rate (68.8 vs. 79.8%), ongoing pregnancy rate (65.9 vs. 72.6%), and miscarriage rate (4.2 vs. 8.8%), respectively. Conclusion: Sperm DNA fragmentation on the day of ICSI is not associated with embryologic or clinical outcomes after euploid blastocyst transfer. Increasing levels of SDF are associated with low sperm concentration and total motile sperm count. [ABSTRACT FROM AUTHOR]

Purpose: To explore clinical benefit of performing two intrauterine inseminations (IUI) 24 h apart—a double IUI vs. a single IUI among lesbian and single women. Methods: Retrospective cohort study using electronic medical record review during a 17-year period (11/1999–3/2017). A total of 11,396 patients at a single academic-affiliated private practice were included in this study. All cycles with a single or double IUI were included. A sub-analysis of first cycles only (n = 10,413) was also performed. Canceled IVF cycles converted to IUI were excluded. T tests and Wilcoxon rank-sum tests were used for continuous data, and chi-square for categorical data. Multivariable logistic regression controlled for patient age, day 3 follicle-stimulating hormone (D3 FSH), body mass index (BMI), peak estradiol (E2), and post-wash total motile sperm counts to model the association between IUI number and ongoing pregnancy rate (OPR) according to sperm source (autologous vs. donor). Generalized estimating equations and mixed effect models accounted for multiple cycles from the same woman. Adjusted odds ratio (AOR) with 95% CI was determined. Sub-analyses of sexual orientation and partner status were performed to compare heterosexual couples with proven infertility to women with lesbian and single women. Results: During the study period, 22,452 cycles met inclusion criteria (single IUI 1283 vs. double IUI 21,169). Mean patient age and BMI were similar between groups. For couples using autologous sperm, OPR was significantly higher with double IUI (12.0% vs. 14.1%; p = 0.0380). A similar increase was observed for donor sperm OPR among heterosexual couples (14.4% vs. 16.2%), though this did not reach statistical significance (p = 0.395). A sub-analysis restricted to donor sperm demonstrates a clinical benefit of second IUI in heterosexual couples, 8.5% vs. 17.6% OPR (AOR 2.94; CI 1.00–10.99; p = 0.0496). When lesbian and single patients were evaluated, there was no difference (17.2% vs. 15.2%; AOR 0.99; CI 0.59–1.70; p = 0.0958). Conclusions: Double IUI is associated with a significantly higher OPR for heterosexual couples using an autologous or donor sperm source. The benefit of a second IUI is less clear in patients with undocumented fertility status using donor sperm, such as single and lesbian women. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the systematic review is to describe the obstetrical complications associated with pregnancies in the context of a thin endometrial lining. Methods: Systematic review of the literature. Results: Patients who conceive in the setting of a thin endometrium have a significantly increased risk of early pregnancy loss, namely miscarriage and ectopic pregnancy. These patients also have a twofold increase in low birth weight and preterm delivery, as well as a significantly higher risk of intrauterine growth restriction and composite adverse perinatal outcomes. Conclusions: In addition to the lower probability of conception, a thin endometrium in assisted reproductive technologies appears to be associated with both early and late pregnancy complications. These pregnancies thus warrant special attention and close follow-up from obstetricians. [ABSTRACT FROM AUTHOR]

Purpose: To elicit patient preferences for social media utilization and content in the infertility clinic.Methods: This was a cross-sectional survey study conducted in three US fertility practices. Women presenting to the infertility clinic for an initial or return visit were offered an anonymous voluntary social media survey. The survey elicited patient perception of whether social media use in the infertility clinic is beneficial, and preferences regarding topics of interest.Results: A total of 244 surveys were collected during the study period, of which 54.5% were complete. Instagram is a more popular platform than Twitter across all age groups. Use of both platforms varies by age, with patients ≥ 40 less likely to be active users. The majority of respondents felt that social media provided benefit to the patient experience in the infertility clinic (79.9%). “Education regarding infertility testing and treatment” and “Myths and Facts about infertility” were the most popular topics for potential posts, with 93.4 and 92.0% of patients endorsing interest respectively. The least popular topic was “Newborn photos and birth announcements,” with only 47.4% endorsing interest. A little over half of respondents (56.3%) would feel comfortable with the clinic posting a picture of their infant. The vast majority of patients (96.2%) feel comfortable communicating electronically with their infertility clinic.Conclusion: Patients are interested in the use of social media as a forum for patient education and support in the infertility clinic. Patient preferences regarding post topics should be carefully considered. [ABSTRACT FROM AUTHOR]

Purpose: Dehydroepiandrosterone (DHEA) is often prescribed for poor responders in IVF in an effort to improve response to ovarian stimulation. The effect of DHEA supplementation and resultant supraphysiologic DHEA-S serum levels on sex steroid assays has not been evaluated in this population. This study seeks to determine the relationship between DHEA supplementation and progesterone measurements to characterize the degree of interference with particular immunoassays. Methods: Characterization was accomplished in two phases. First, DHEA-S standard control reagents with no progesterone present were assayed for both DHEA-S and progesterone levels. Second, serum pools from 60 unique IVF patients' serum were used to create six pooled serum samples: three from patients on DHEA supplementation and three from patients not on DHEA supplementation. The three pools were composed of patients whose serum fell into low, medium, and high progesterone ranges. Baseline DHEA-S and progesterone were measured, and the mean level of DHEA-S in the mid-range progesterone pool was used as the mid-point for addition of DHEA-S standard to the serum pools from patients without DHEA supplementation. Progesterone from these pools was then measured on three commercially available immunoassay systems. Results: The first experiment revealed a linear increase in progesterone when analyzing the DHEA-S standard ranging from 0.5 ng/mL in the blank control (no DHEA-S) to up to 2.0 ng/mL in the high control (DHEA-S >700 μg/mL), indicating that the DHEA-S cross-reacts with the progesterone assays. In the second experiment, patients' serum DHEA-S and progesterone were measured from pooled serum samples of those taking DHEA and those not taking DHEA. Adding DHEA-S to the pooled serum of those not taking DHEA resulted in a linear increase in progesterone levels on two of three commercially available immunoassays ( p < 0.05). Conclusions: DHEA-S can interfere with standard progesterone immunoassays used in clinical ART programs, and thus serum progesterone levels in IVF patients on DHEA supplementation may not reflect truly bioactive progesterone. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study is to determine if thrombophilic single nucleotide polymorphisms (SNPs) affect outcomes in fresh in vitro fertilization (IVF) cycles in a large general infertility population. Methods: A prospective cohort analysis was performed at a university-affiliated private IVF center of female patients undergoing fresh non-donor IVF cycles. The effect of the following thrombophilic SNPs on IVF outcomes were explored: factor V (Leiden and H1299R), prothrombin (G20210A), factor XIII (V34L), β-fibrinogen (-455G → A), plasminogen activator inhibitor-1 (4G/5G), human platelet antigen-1 (a/b9L33P), and methylenetetrahydrofolate reductase (C677T and A1298C). The main outcome measures included positive pregnancy test, clinical pregnancy, embryo implantation, live birth, and pregnancy loss. Results: Patients (1717) were enrolled in the study, and a total of 4169 embryos were transferred. There were no statistically significant differences in positive pregnancy test, clinical pregnancy, embryo implantation, live birth, or pregnancy loss in the analysis of 1717 patients attempting their first cycle of IVF. Receiver operator characteristics and logistic regression analyses showed that outcomes cannot be predicted by the cumulative number of thrombophilic mutations present in the patient. Conclusions: Individual and cumulative thrombophilic SNPs do not affect IVF outcomes. Therefore, initial screening for these SNPs is not indicated. [ABSTRACT FROM AUTHOR]

Purpose: The ideal thyroid-stimulating hormone (TSH) range for infertile women attempting conception has not been determined. Current recommendations include optimizing the preconception TSH value to ≤2.5 mIU/L, which is the established goal for pregnant women. The aim of this study was to determine if there is a distinct range of TSH ≤2.5 mIU/L for infertile women undergoing in vitro fertilization (IVF) that improves reproductive outcomes. Methods: One thousand five hundred ninety-nine euploid blastocyst transfer cycles were evaluated in which TSH measurements were obtained 8 days after embryo transfer. Only euploid embryo transfers were included in an effort to control for embryo quality. Patients were separated into TSH groups utilizing 0.5 mIU/L increments. Implantation, live birth, and miscarriage rates among the TSH groups were compared. Outcomes for individuals on thyroid hormone supplementation and those not requiring supplementation were evaluated. Results: There was no difference in implantation ( p = 0.56), live birth ( p = 0.36), or miscarriage rates ( p = 0.10) between TSH groups. Receiver operating characteristic (ROC) curves for implantation, live birth, and miscarriage approached the line of no discrimination, signifying that there is no value of TSH within the recommended range for pregnancy (≤2.5 mIU/L) that predicts IVF outcomes better than other values in this range. Live birth rates for patients requiring thyroid hormone supplementation and those not on medication were similar ( p = 0.86). Conclusions: The recommended TSH range for pregnancy (≤2.5 mIU/L) may be applied to infertile patients attempting conception without a need for further adjustment. [ABSTRACT FROM AUTHOR]

Purpose: To assess the impact of single pass outpatient endometrial biopsy in patients at the highest risk for an endometrial cause for failed implantation; those that have failed to conceive despite the transfer of morphologically normal euploid embryos. Methods: This is a retrospective cohort study consisting of all patients less than 42 years old who failed their first euploid blastocyst transfer and subsequently completed a second transfer cycle of euploid blastocysts. Cycles were analyzed to determine if a single pass endometrial biopsy, termed 'endometrial disruption', was performed in a cycle preceding their second embryo transfer. Transfer outcomes were analyzed and implantation rates calculated. Data analysis was performed to compare outcomes between patients who had endometrial disruption performed versus those that did not. Results: Two hundred ninety patients failed their first euploid embryo transfer and subsequently completed a second euploid embryo transfer and were included. Thirty-nine patients underwent endometrial disruption and 251 did not. There were no statistical differences in clinical implantation rate or sustained implantation rate between the group with endometrial disruption and subjects without any intervention (Clinical IR, 43.6 % vs. 55.0 %, p = 0.13; 38.5 % vs. 42.6 %, p = 0.60). When controlling for transfer order there was no statistical difference noted in implantation rates. Conclusions: Single pass endometrial biopsy has no impact on endometrial receptivity in the highest risk subgroup- patient's that have failed to sustain the transfer of morphologically normal euploid embryos- as evidenced by equivalent implantation rates. It is possible that variations in technique may alter outcomes and randomized trials are needed to answer this question. [ABSTRACT FROM AUTHOR]

Purpose: To characterize each chromosome's risk for being involved in embryonic aneuploidy. Methods: This is a retrospective cohort study conducted at a single, academic center. The cohort consisted of 15,169 consecutive trophectoderm biopsies which then underwent comprehensive chromosome screening utilizing validated real-time polymerase chain reaction (RT-PCR) or single nucleotide polymosphism (SNP) array platforms. Analysis was done to determine probability of aneuploidy by chromosome, changes in that risk with increasing maternal age, and in relationship of aneuploidy to chromosomal structure as classified by prior cytogenetic literature. Results: The highest prevalence of imbalances leading to aneuploidy was seen for chromosomes 13, 15, 16, 18, 19, 21, and 22. While elevated in all age groups, there was a disproportionate rise in aneuploidy rates for these chromosomes with increasing maternal age. When classic cytogenetic karyotype groups were compared, the overall smaller groups D, E, and G were associated with the highest rates. Similarly, when grouped based upon structure, acrocentric chromosomes exhibited the highest rates of aneuploidy, followed by the metacentric chromosomes, with the lowest prevalence of error in those with submetacentric structures. Conclusions: The highest rates of chromosomal aneuploidy were found in chromosomes known to be involved in clinically detectable, abnormal pregnancies, not just simply implantation failure. The rate of aneuploidy in these chromosomes rises disproportionately with age when compared to the other chromosomes which may provide information about chromosomal susceptibility to aging. The biological structure groupings did show varied aneuploidy rates which may provide insight into the biology of aneuploidy. [ABSTRACT FROM AUTHOR]