Macroprolactinemia: a mini-review and update on clinical practice.

Hyperprolactinemia is common among infertile patients, with up to 15%-20% of women with oligomenorrhea having hyperprolactinemia. Suppression of the hypothalamic-pituitary-gonadal axis via inhibition of pulsatile gonadotropin releasing hormone because of hyperprolactinemia is a common endocrine etiology of infertility. There are 3 forms of human prolactin (PRL): monomeric PRL, dimeric PRL, and macro-PRL. Also known as big-big PRL, macro-PRL has a molecular weight >150 kDa and normally comprises 5%-10% of circulating PRL. When the predominant form of circulating PRL is macro-PRL, macroprolactinemia is diagnosed. Among patients with hyperprolactinemia, 10%-46% have macroprolactinemia. Patients with macroprolactinemia are at risk of unnecessary pituitary imaging and treatment with dopamine agonists if not correctly diagnosed. Given the high prevalence of macroprolactinemia among patients with elevated PRL levels and the different management of patients with macroprolactinemia vs true monomeric hyperprolactinemia, all patients with persistently elevated PRL levels should be screened for macro-PRL.

The association of obesity with euploidy rates in women undergoing in vitro fertilization with preimplantation genetic testing.

PURPOSE: The purpose of this study was to determine the impact of body mass index (BMI) on euploidy rates for in vitro fertilization (IVF) cycles with preimplantation genetic testing (PGT) utilizing primarily next-generation sequencing (NGS). METHODS: This retrospective cohort study included women aged ≤ 45 years who underwent IVF/PGT between September 2013 and September 2020 at a single university-affiliated fertility center. The primary outcome was euploidy rate. Secondary outcomes included peak serum estradiol (E2), number of oocytes retrieved, oocyte maturation rate, high-quality blastulation rate, clinical loss rate (CLR), clinical pregnancy rate (CPR), and ongoing pregnancy/live birth rate (OPR/LBR). RESULTS: The study included 1335 IVF cycles that were stratified according to BMI (normal, n = 648; overweight, n = 377; obese, n = 310). The obese group was significantly older with significantly lower baseline FSH, peak E2, high-quality blastulation rate, and number of embryos biopsied than the normal group. Overall euploidy rates were not significantly different between BMI groups (normal 36.4% ± 1.3; overweight 37.3% ± 1.8; obese 32.3% ± 1.8; p = 0.11), which persisted after controlling for covariates (p = 0.82) and after stratification of euploidy rate by age group and by number of oocytes retrieved per age group. There were no significant differences in CLR, CPR, and OPR/LBR across BMI groups. CONCLUSIONS: Despite a lower high quality blastulation rate with obesity, there is not a significant difference in euploidy rates across BMI groups in women undergoing IVF/PGT.

Pregnancy outcomes after frozen-thawed embryo transfer using letrozole ovulation induction, natural, or programmed cycles.

OBJECTIVE: To evaluate and compare pregnancy outcomes between letrozole ovulation induction, natural, and programmed frozen-thawed embryo transfer (FET) cycles in a population based in the United States. DESIGN: Retrospective cohort study. SETTING: Single university-affiliated infertility practice. PATIENT(S): A total of 3,148 FET cycles consisting of patients aged ≤45 years transferring blastocysts that were created from autologous oocytes between January 2015 and July 2021. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was the ongoing pregnancy rate (OPR) or live birth rate (LBR). The secondary outcomes included clinical pregnancy and clinical loss rates (CLRs). RESULT(S): The OPR/LBR was higher among letrozole FETs than among programmed FETs (adjusted risk ratio [aRR] 1.11, 95% confidence interval [CI] 1.02-1.21) but comparable to natural FETs (aRR 1.05, 95% CI 0.96-1.14). The OPR/LBR was comparable between natural and programmed FETs (aRR 1.06, 95% CI 0.99-1.13). The CLR was lower in the natural FET group than in the programmed FET group (aRR 0.62, 95% CI 0.46-0.84). There were no differences in CLRs between letrozole and programmed FETs and between letrozole and natural FETs. Among ovulatory women, the OPR/LBR among letrozole FETs was higher than that among programmed FETs (aRR 1.16, 95% CI 1.05-1.28). The CLR among ovulatory women was significantly lower in both letrozole FETs (aRR 0.44, 95% CI 0.22-0.87) and natural FETs (aRR 0.59, 95% CI 0.43-0.80) than in programmed FETs. Among anovulatory women, the OPR/LBR in the letrozole FET group was similar to that in the programmed FET group (aRR 0.95, 95% CI 0.79-1.13). CONCLUSION(S): Letrozole and natural FET clinical outcomes were improved compared with programmed FET outcomes.

Embryologic outcomes among patients using a microfluidics chip compared to density gradient centrifugation to process sperm: a paired analysis.

PURPOSE: To evaluate embryologic outcomes among paired IVF cycles in which a microfluidics chip was utilized compared to density gradient centrifugation for sperm processing. METHODS: This was a retrospective cohort study of 88 paired IVF cycles from patients aged 18-44 years at a university-affiliated IVF center. Fresh cycles from patients undergoing ICSI with sperm processed by a microfluidics chamber (microfluidics cycles) were compared to the same patients' previous ICSI cycles in which sperm was processed via density gradient centrifugation (control cycles). The primary outcome was the high-quality blastulation rate. RESULTS: High-quality blastulation rate per oocyte retrieved was significantly higher in the microfluidics group compared to the control group (21.1% versus 14.5%, p < 0.01) as was the blastulation rate per 2PN (42.7% versus 30.8%, p < 0.01). Fertilization rates were significantly higher in the microfluidics group. The euploidy rate per oocyte retrieved was significantly higher in the microfluidics group compared with the control group (8.5% versus 4.3%, p = 0.04), while the euploidy rate per embryo biopsied was comparable (32.6% versus 21.8%, p = 0.09). In patients with male factor infertility, the high-quality blastulation rate was similar between the control and microfluidics cycles. There was a significantly higher blastulation rate among microfluidics cycles in patients without a diagnosis of male factor infertility (p < 0.01). CONCLUSION: In this study, several embryologic outcomes, including fertilization rate, high-quality blastulation rate, and euploidy rate, were significantly higher in the microfluidics group compared to the control group. Microfluidics sperm processing may be a way to improve embryologic outcomes.

Reduction in multiple pregnancy rate in donor oocyte-recipient gestational carrier (GC) in vitro fertilization (IVF) cycles in the USA with single-embryo transfer and preimplantation genetic testing.

PURPOSE: To evaluate the utilization of single-embryo transfer (SET) and preimplantation genetic testing (PGT) in gestational carrier IVF cycles in the USA with donor oocyte and examine the impact on live birth and multiple gestation. METHODS: Retrospective cohort study using the Society of Assisted Reproductive Technology (SART) clinic database of 4776 donor oocyte-recipient IVF cycles in which a GC was used. The cycles were separated into 4 groups by use of PGT and number of embryos transferred as follows: (1) PGT and single-embryo transfer (PGT-SET); (2) PGT and multiple embryo transfer (PGT-MET); (3) no PGT and SET (NoPGT-SET); (4) no PGT and MET (NoPGT-MET). Primary outcomes were live birth rate (LBR) and multiple pregnancy rate (MPR). RESULTS: More than one blastocyst was transferred in 48.7% (2323/4774) of the cycles. When ≥1 blastocyst was transferred, with or without the use of PGT, the MPR was 45.5% and 42.0%, respectively. In comparison, in the PGT-SET and NoPGT-SET groups, the MPR was 1.4% (8/579) and 3.3% (29/883), respectively. Live birth rates increased with the use of PGT-A and with MET. CONCLUSION: This study shows that SET, with or without PGT, is associated with a significantly reduced MPR in donor oocyte-recipient GC IVF cycles while maintaining high LBR. It also demonstrates that many infertility centers in the USA are not adhering to ASRM embryo transfer guidelines. Our findings highlight an opportunity to increase GC safety, which ultimately may lead to widened access to this increasingly restricted service outside the USA.

Impact of trophectoderm biopsy on obstetric and perinatal outcomes following frozen-thawed embryo transfer cycles.

STUDY QUESTION: Does trophectoderm biopsy for preimplantation genetic testing (PGT) increase the risk of obstetric or perinatal complications in frozen-thawed embryo transfer (FET) cycles? SUMMARY ANSWER: Trophectoderm biopsy may increase the risk of hypertensive disorders of pregnancy (HDP) in pregnancies following FET cycles. WHAT IS KNOWN ALREADY: Trophectoderm biopsy has replaced blastomere biopsy as the standard of care to procure cells for PGT analysis. Recently, there has been concern that trophectoderm biopsy may adversely impact obstetric and perinatal outcomes. Previous studies examining this question are limited by use of inappropriate control groups, small sample size or reporting on data that no longer reflects current IVF practice. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study conducted at a single university-affiliated fertility center. A total of 756 patients who underwent FET with transfer of previously vitrified blastocysts that had either trophectoderm biopsy or were unbiopsied and resulted in a singleton live birth between 2013 and 2019 were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Obstetric and perinatal outcomes for patients aged 20-44 years who underwent FET with transfer of previously vitrified blastocysts that were either biopsied (n = 241) or unbiopsied (n = 515) were analyzed. Primary outcome was odds of placentation disorders including HDP and rate of fetal growth restriction (FGR). Binary logistic regression was performed to control for potential covariates. MAIN RESULTS AND THE ROLE OF CHANCE: The biopsy group was significantly older, had fewer anovulatory patients, was more often nulliparous and had fewer embryos transferred compared to the unbiopsied group. After controlling for potential covariates, the probability of developing HDP was significantly higher in the biopsy group compared with unbiopsied group (adjusted odds ratio (aOR) 1.943, 95% CI 1.072-3.521; P = 0.029).There was no significant difference between groups in the probability of placenta previa or placenta accreta. There was also no significant difference in the rate of FGR (aOR 1.397; 95% CI, 0.815-2.395; P = 0.224) or the proportion of low (aOR 0.603; 95% CI, 0.336-1.084; P = 0.091) or very low (aOR 2.948; 95% CI, 0.613-14.177; P = 0.177) birthweight infants comparing biopsied to unbiopsied groups. LIMITATIONS, REASON FOR CAUTION: This was a retrospective study performed at a single fertility center, which may limit the generalizability of our findings. WIDER IMPLICATIONS OF THE FINDINGS: Trophectoderm biopsy may increase the risk of HDP in FET cycles, however, a prospective multicenter randomized trial should be performed to confirm these findings. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was obtained for this study. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: NA.

Maternal and perinatal outcomes in programmed versus natural vitrified-warmed blastocyst transfer cycles.

RESEARCH QUESTION: Do maternal and perinatal outcomes differ between natural and programmed frozen embryo transfer (FET) cycles? DESIGN: Retrospective cohort study at a university-affiliated fertility centre including 775 patients who underwent programmed or natural FET cycles resulting in a singleton live birth using blastocysts vitrified between 2013 and 2018. RESULTS: A total of 384 natural and 391 programmed FET singleton pregnancies were analysed. Programmed FET resulted in higher overall maternal complications (32.2% [126/391] versus 18.8% [72/384]; P < 0.01), including higher probability of hypertensive disorders of pregnancy (HDP) (15.3% [60/391] versus 6.3% [24/384]; P < 0.01), preterm premature rupture of membranes (2.6% [10/391] versus 0.3% [1/384]; P = 0.02) and caesarean delivery (53.2% [206/387] versus 42.8% [163/381]; P = 0.03) compared with natural FET. After controlling for potential confounders, including age, body mass index, parity, smoking status, history of diabetes or chronic hypertension, infertility diagnosis, number of embryos transferred and use of preimplantation genetic testing, the adjusted odds ratio for HDP was 2.39 (95% CI 1.37 to 4.17) and for overall maternal complications was 2.21 (95% CI 1.51 to 3.22) comparing programmed with natural FET groups. The groups did not significantly differ for any perinatal outcomes analysed, including birth weight (3357.9 ± 671.6 g versus 3318.4 ± 616.2 g; P = 0.40) or rate of birth defects (1.5% [6/391] versus 2.1% [8/384]; P = 0.57), respectively. CONCLUSION: Vitrified-warmed blastocyst transfer in a programmed cycle resulted in a twofold higher probability of HDP compared with transfer in a natural cycle. Natural FET cycle should, therefore, be recommended as first line for all eligible patients undergoing FET to reduce the risk of HDP.

Pregnancy outcomes after frozen-thawed single euploid blastocyst transfer following IVF cycles using GNRH agonist or HCG trigger for final oocyte maturation.

PURPOSE: To assess whether GnRH agonist trigger impacts the implantation potential of euploid embryos. METHODS: Retrospective cohort study done at an academic IVF center evaluating frozen-thawed embryo transfer (FET) cycles in which single-euploid blastocysts were transferred between 2014 and 2019. All embryos were generated in an IVF cycle which used GnRHa or hCG trigger and then were transferred in a programmed or natural FET cycle. Only the first FET cycle was included for each patient. Primary outcome was ongoing pregnancy rate or live birth rate (OPR/LBR). Secondary outcomes were implantation rate (IR), clinical pregnancy rate (CPR), clinical loss rate (CLR), and multiple pregnancy rate (MPR). Logistic regression was performed to control for confounding variables. A p value of < 0.05 was considered statistically significant. RESULTS: Two hundred sixty-three FET cycles were included for analysis (GnRHa = 145; hCG = 118). The GnRHa group was significantly younger (35.2 vs. 37.5 years) and had higher AMH values (4.50 ng/ml vs. 2.03 ng/ml) than the hCG group, respectively (p < 0.05). There was no significant difference in OPR/LBR (64.1% (93/145) vs. 65.3% (77/118); p = 0.90) between the GnRHa and hCG groups, respectively. There was also no significant difference in IR, CPR, CLR, or MPR between groups. After controlling for confounding variables, the adjusted odds ratio for OPR/LBR was 0.941 (95% CI, 0.534-1.658); p = 0.83) comparing GnRHa to hCG. Pregnancy outcomes did not significantly differ when groups were stratified by age (< 35 vs. > 35 years old). CONCLUSIONS: Our findings confirm that euploid embryos created after hCG or GnRHa trigger have the same potential for pregnancy.

In vitro fertilization outcomes after preimplantation genetic testing for chromosomal structural rearrangements comparing fluorescence in-situ hybridization, microarray comparative genomic hybridization, and next-generation sequencing.

OBJECTIVE: To compare in vitro fertilization (IVF) outcomes for preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) using various testing platforms. DESIGN: Retrospective cohort. SETTING: Large academic IVF center. PATIENTS: Fifty-one balanced translocation carriers undergoing IVF with PGT-SR who completed a total of 91 cycles, including 31 fluorescence in-situ hybridization (FISH), 24 microarray comparative genomic hybridization (aCGH), and 36 next-generation sequencing (NGS) testing cycles. INTERVENTIONS: PGT-SR. MAIN OUTCOME MEASURES: Primary outcome of live-birth rate and secondary outcomes including implantation rate, clinical loss rate, and percentages of normal or balanced, unbalanced, and aneuploid embryos detected. RESULTS: There was no statistically significant difference in LBR, though there was a tendency toward a higher LBR for NGS testing (14 of 19, 73.7%) compared with FISH (8 of 18, 44.4%) and aCGH (10 of 20, 50.0%). The implantation rate was statistically significantly higher for NGS (16 of 20, 80.0%) compared with FISH (11 of 25, 44.0%) and aCGH (16 of 30, 53.3%). There was no statistically significant difference in clinical pregnancy losses. There was a lower percentage of normal or balanced embryos with FISH (12.5%) compared with aCGH (23.7%) and with NGS (20.7%). CONCLUSIONS: This is the first report of PGT-SR outcomes for translocation carriers directly comparing PGT-SR using FISH, aCGH, and NGS. Our findings suggest an improvement in pregnancy outcomes parallel to the advancement in technology and are reassuring for continued use of NGS for this population.

The window is wide: flexible timing for vitrified-warmed embryo transfer in natural cycles.

RESEARCH QUESTION: What is the optimal timing for transfer in natural cycle vitrified-warmed embryo transfers (NC-VET)? DESIGN: This retrospective cohort study uses data from a large university-affiliated IVF clinic. The study included 341 NC-VET cycles with autologous oocytes and non-preimplantation genetic testing, vitrified embryos from January 2013 to September 2017. Each cycle was classified by timing of embryo transfer in relation to LH surge ≥20 IU/l. Group 1: LH ≥20 IU/l one day and blastocyst was transferred 6 days later; Group 2: LH ≥20 IU/l two consecutive days and blastocyst was transferred 6 days after the initial surge; Group 3: LH ≥20 IU/l two consecutive days and blastocyst was transferred 7 days after the initial surge. The primary outcome was ongoing pregnancy rate (OPR). The secondary objective was to compare OPR in relation to serum oestradiol dynamics and progesterone concentration (according to threshold 1.0 ng/ml) 6 days prior to embryo transfer. RESULTS: OPR were similar for all three groups (66.8%, 65.0%, 62.9% for Groups 1, 2 and 3, respectively). When stratified according to oestradiol and progesterone, no significant differences were noted in OPR. CONCLUSIONS: The results suggest that the timing of blastocyst transfer in a natural cycle after LH surge is flexible within 24 h. Outcomes are equally good with day of embryo transfer 6 or 7 days after LH surge date. Oestradiol dynamics and progesterone concentration 6 days prior to NC-VET did not have a significant impact on OPR.

Independent serum markers of corpora lutea function after gonadotropin-releasing hormone agonist trigger and adjuvant low dose human chorionic gonadotropin in in vitro fertilization.

OBJECTIVE: To characterize corpora lutea (CL) function after gonadotropin-releasing hormone agonist (GnRHa) trigger with the use of adjuvant human chorionic gonadotropin (hCG). DESIGN: Secondary analysis of serum from prospective randomized clinical trial. SETTING: University-based fertility center. PATIENT(S): Women under 40 years of age at risk of ovarian hyperstimulation syndrome (OHSS) with serum E2 level <4,000 pg/mL. INTERVENTIONS(S): All subjects underwent ovarian stimulation with the use of a GnRH antagonist protocol. Within a larger study, subjects were randomized to receive 1,000 IU hCG at the time of GnRHa trigger and placebo at the time of vaginal oocyte retrieval (VOR) or placebo at the time of GnRHa trigger and 1,500 IU hCG at the time of VOR. MAIN OUTCOME MEASURE(S): Luteal phase and early pregnancy curves of serum prorenin and 17α-hydroxyprogesterone (17OH-P). RESULT(S): Thirty subjects enrolled in this secondary analysis. Serum 17OH-P peaked in the early luteal phase, 5 days after GnRHa trigger, with a nadir in the mid-luteal phase 9 days after trigger. Serum prorenin peaked in the luteal phase 2 days after GnRHa trigger, independently from adjuvant hCG timing, and reached a nadir at 9 days after trigger. CL function appears higher when adjuvant hCG is given at VOR compared with adjuvant hCG given at the time of trigger. CONCLUSION(S): CL function, as interpreted by proxy measures of serum prorenin and 17OH-P with pregnancy, continues despite GnRHa trigger. Both options for adjuvant hCG timing are sufficient for CL rescue and successful pregnancy, so the potential for OHSS risk with increased CL activity after hCG at VOR should be considered. CLINICAL TRIAL REGISTRATION NUMBER: NCT01815138.

Euploidy rates between cycles triggered with gonadotropin-releasing hormone agonist and human chorionic gonadotropin.

OBJECTIVE: To evaluate differences in euploidy rates between IVF cycles triggered with either GnRH agonist (GnRHa) or hCG. DESIGN: Retrospective cohort study. SETTING: University-affiliated fertility center. PATIENT(S): A total of 366 patients performing 539 IVF cycles utilizing preimplantation genetic testing for aneuploidy (PGT-A). INTERVENTION(S): Gonadotropin-releasing hormone agonist or hCG trigger of oocyte maturation during IVF cycles. MAIN OUTCOME MEASURE(S): Rate of euploid embryos. RESULT(S): Patients in the GnRHa trigger arm were younger, with a lower body mass index and higher antimüllerian hormone level, and they had a higher number of oocytes retrieved and embryos biopsied. Euploid rate per embryo biopsied was higher after GnRHa trigger than after hCG trigger (37.8% ± 2.1% vs. 30.3% ± 1.8%), but multivariate regression analysis controlling for potential confounding factors did not show any differences between the two groups. Moreover, the euploid rate per oocyte retrieved was not significantly different overall (GnRHa vs. hCG: 33.9% ± 2.2% vs. 28.0% ± 1.9%). The anticipated decline in the rate of euploid embryos per oocyte retrieved went from 15.8% ± 1.2% for age <35 years to 4.3% ± 0.9% for patients aged ≥41 years. There were no significant differences between the two groups after stratifying by age and controlling for PGT-A testing modality. CONCLUSION(S): Both GnRHa and hCG trigger result in comparable euploid rates. Trigger with GnRHa should therefore be considered a valid option for trigger modality in freeze-all PGT-A cycles, in view of its demonstrated effectiveness and known safety enhancement.

Longitudinal profiling of human blood transcriptome in healthy and lupus pregnancy.

Systemic lupus erythematosus carries an increased risk of pregnancy complications, including preeclampsia and fetal adverse outcomes. To identify the underlying molecular mechanisms, we longitudinally profiled the blood transcriptome of 92 lupus patients and 43 healthy women during pregnancy and postpartum and performed multicolor flow cytometry in a subset of them. We also profiled 25 healthy women undergoing assisted reproductive technology to monitor transcriptional changes around embryo implantation. Sustained down-regulation of multiple immune signatures, including interferon and plasma cells, was observed during healthy pregnancy. These changes appeared early after embryo implantation and were mirrored in uncomplicated lupus pregnancies. Patients with preeclampsia displayed early up-regulation of neutrophil signatures that correlated with expansion of immature neutrophils. Lupus pregnancies with fetal complications carried the highest interferon and plasma cell signatures as well as activated CD4+ T cell counts. Thus, blood immunomonitoring reveals that both healthy and uncomplicated lupus pregnancies exhibit early and sustained transcriptional modulation of lupus-related signatures, and a lack thereof associates with adverse outcomes.

Frozen blastocyst transfer outcomes in immediate versus delayed subsequent cycles following GnRH agonist or hCG triggers.

PURPOSE: The aim of this study is to analyze clinical pregnancy rates (CPR) and ongoing pregnancy rates (OPR) for frozen embryo transfers (FET) performed with blastocysts in the cycle immediately after GnRH agonist (GnRHa) versus human chorionic gonadotropin (hCG) triggers, with outcomes of delayed FET for comparison. METHODS: Retrospective cohort study at a university-affiliated in vitro fertilization (IVF) clinic, including patients undergoing IVF between 2013-16 with a blastocyst FET performed within two menstrual cycles of a previous stimulation cycle and vaginal oocyte retrieval (VOR). FETs included programmed and natural endometrial preparation. Outcome measures were clinical and ongoing pregnancy rates. RESULTS: CPR and OPR for 344 FET cycles were similar when comparing immediate and delayed transfer overall (crude CPR 67.5 versus 76.5%, p = 0.11; OPR 57.5 versus 66.7%, p = 0.13), and after stratifying by cycles following hCG trigger (OPR 62.5 versus 66.3%, p = 0.61) and GnRHa trigger (OPR 55.6 versus 64.5%, p = 0.17). When considering a number of predictors for OPR, an adjusted odds ratio (OR) of 1.74 [95% CI 1.00-3.03] approached significance in favor of delayed FET. CONCLUSIONS: Regardless of trigger modality, patients can be reassured that pregnancy rates with FET are high in immediate and delayed cycles. However, our study suggests a potential benefit in delaying a cycle before proceeding with FET.

Freeze-only versus fresh embryo transfer in a multicenter matched cohort study: contribution of progesterone and maternal age to success rates.

OBJECTIVE: To compare implantation and ongoing pregnancy rates in freeze-only versus fresh transfer cycles. DESIGN: Retrospective matched cohort study. SETTING: Not applicable. PATIENT(S): Women selected using a matching algorithm for similar distributions of clinical characteristics for a total of 2,910 cycles (1,455 fresh cohort and 1,455 freeze-only cohort). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation and ongoing pregnancy rates. RESULT(S): Implantation and ongoing pregnancy rates were statistically significantly higher in the freeze-only transfer cohort than in the matched fresh transfer cohort: ongoing pregnancy rate for freeze-only was 52.0% (95% confidence interval [CI], 49.4-54.6) and for fresh was 45.3% (95% CI, 42.7-47.9), odds ratio (OR) 1.31 (95% CI, 1.13-1.51). In a stratified analysis, the odds of ongoing pregnancy after freeze-only transfer were statistically significantly higher for women both above and below age 35 with progesterone concentration >1.0 ng/mL (age ≤35: OR 1.38 [1.11-1.71]; age >35: OR 1.73 [1.34-2.24]). For women with progesterone concentration ≤1.0 ng/mL, no statistically significant difference in freeze-only odds of ongoing pregnancy was observed in either age group. The sensitivity analysis revealed that increasing maternal age alone (regardless of progesterone) trended toward a more beneficial effect of freeze-only cycles. A lower progesterone concentration was associated with statistically significantly higher ongoing pregnancy odds for fresh but not freeze-only cycles. CONCLUSION(S): Freeze-only transfer protocols are associated with statistically significantly higher ongoing implantation and pregnancy rates compared with fresh transfer cycles. This effect is most pronounced for cycles with progesterone >1.0 ng/mL at trigger and may also be stronger for older patients.

Detection of an Inherited Deletion in Products of Conception in a Patient With Recurrent Losses and Normal Karyotype.

BACKGROUND: Microarray analysis testing on products of conception can provide valuable information in the evaluation of recurrent pregnancy loss beyond ploidy status. CASE: A maternally inherited deletion on the X chromosome was detected by microarray analysis performed on products of conception in a couple with recurrent pregnancy loss. The mother had a previously demonstrated normal karyotype with standard cytogenetic analysis but was subsequently determined to have the same X chromosome deletion by oligonucleotide single-nucleotide polymorphism (SNP) microarray analysis. CONCLUSION: Direct testing of products of conception using oligonucleotide SNP microarray identified a maternally inherited microdeletion on the X chromosome in a patient with recurrent losses and normal karyotype. Going forward, the couple may use preimplantation genetic diagnosis testing to identify embryos free of this deletion for transfer.

Pregnancy rates for single embryo transfer (SET) of day 5 and day 6 blastocysts after cryopreservation by vitrification and slow freeze.

PURPOSE: The purpose of this study was to compare clinical and ongoing pregnancy rates in cycles with single embryo transfer (SET) of blastocysts cryopreserved on day 5 or day 6. Our aim was to determine whether day 6 blastocysts perform adequately to recommend SET. METHODS: Retrospective cohort study including 468 transfer cycles for 392 women younger than age 38 undergoing SET at a university-affiliated IVF clinic in the USA. A total of 261 day 5 blastocysts and 207 day 6 blastocysts for frozen-thawed SET between 2010 and 2016 were analyzed. Data included cryopreservation by both a slow freeze method and vitrification. RESULTS: In total, 59.0% of day 5 SET cycles resulted in a clinical pregnancy compared to 54.1% of day 6 blastocysts (p = 0.54). Ongoing pregnancy rates from day 5 frozen-thawed blastocysts (51.7%) were comparable to day 6 (44.9%, p = 0.14). When looking at vitrified blastocysts only, there were no significant differences between day 5 and day 6 blastocysts, with a clinical pregnancy rate of 69.2% for day 5 and 72.5% for day 6 (p = 0.68). CONCLUSIONS: SETs of day 6 cryopreserved blastocysts resulted in similar clinical and ongoing pregnancy rates compared to day 5, particularly after vitrification.

Old habits die hard: retrospective analysis of outcomes with use of corticosteroids and antibiotics before embryo transfer.

OBJECTIVE: To evaluate clinical pregnancy rates in embryo transfer (ET) cycles with and without peri-implantation corticosteroid and oral antibiotic administration. DESIGN: Retrospective cohort study. SETTING: University-affiliated in vitro fertilization (IVF) clinic. PATIENT(S): Eight hundred and seventy-six ETs with or without the routine use of methylprednisolone and doxycycline. INTERVENTION(S): Embryo transfer procedures. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates (CPR). RESULT(S): The CPR with the routine use of methylprednisolone and doxycycline was 56.1% compared with 61.5% after discontinuation of these medications. Ongoing pregnancy rates were 49.5% with medications versus 53.2% without medications. Of the cleavage-stage embryos, 79% underwent assisted hatching; among these, the CPR was 28.7% when treated with corticosteroids and antibiotics compared with 47.4% without medications. CONCLUSION(S): No statistically significant difference in overall IVF outcomes was noted after the discontinuation of routine peri-implantation corticosteroids and antibiotics. The use of these medications varies across the country and may be a result of habit rather than evidence-based medicine.

Increasing awareness of age-related fertility and elective fertility preservation among medical students and house staff: a pre- and post-intervention analysis.

OBJECTIVE: To assess medical students' and house staff's knowledge and personal and professional perceptions of age-related fertility and fertility preservation before and after an educational intervention. DESIGN: Pre-/post intervention survey. SETTING: University-based medical center. PATIENT(S): Medical students and house staff. INTERVENTION(S): An educational session on age-related fertility decline and elective fertility preservation. MAIN OUTCOME MEASURE(S): Knowledge scores and perceptions assessed immediately before and after the intervention. RESULT(S): Sixty-five surveys were administered. Of the 53 respondents, 71.7% were married or in a committed relationship; 89.4% reported that they were delaying childbearing, with career and/or education being the most frequently listed reason (85.7%); 39.5% indicated that they had both personal and professional interest in fertility preservation but identified finances (62.5%) and time (59.4%) as barriers; 86.9% indicated previous exposure, with formal education (80.0%) and social media (40.0%) being the most common sources. Mean scores on a six-question knowledge-based assessment improved significantly following the presentation (54.6 ± 19.0% vs. 78.1 ± 16.0%), as did the number of participants who indicated that they might now recommend elective oocyte cryopreservation to others (71.1% vs. 54.3%). After the intervention, 97.8% thought that it was important for medical professionals to be informed about age-related fertility decline and elective oocyte cryopreservation. CONCLUSION(S): Despite professional and personal interest, knowledge of age-related fertility decline and elective fertility preservation is limited among medical students and house staff. This study highlights the need for formal education across all levels of training and specialties, with even brief interventions being of potential benefit.