Clinical Loss Rate Research Articles

P-532 Understanding the utility of hysteroscopic endometrial peeling in women with implantation failure

Abstract Study question Does hysteroscopic endometrial peeling improve reproductive outcomes in women with implantation failure (IF) undergoing a single euploid embryo transfer (SEET)? Summary answer Women with IF may benefit from intraoperative endometrial peeling prior to a SEET. What is known already Preimplantation genetic testing for embryonic aneuploidy (PGT-A) has been suggested as a strategy to improve implantation rates in women with IF. However, after controlling for the genetic status of the embryo, implantation rates still vary from 40-70%, suggesting that other factors aside from the ploidy of the embryo contribute with the cause of IF. We previously demonstrated that hysteroscopic endometrial peeling enhances implantation in women with IF. However, our study was limited by only including frozen embryo transfers of unscreened embryos. We aim to analyze the clinical utility of hysteroscopic endometrial peeling in women who underwent a SEET. Study design, size, duration A retrospective, cohort study included infertile patients with IF diagnosis who underwent endometrial peeling through hysteroscopy and subsequently a SEET from January 2016 to December 2022. Only the first transfer after the hysteroscopic endometrial peeling was included in the analysis. Participants/materials, setting, methods Women <41 years, with IF, normal saline sonogram, and no previous uterine surgeries were segregated into two groups: A) 66 patients underwent hysteroscopic endometrial peeling, which consists of removing the superficial endometrial layer of the whole uterine cavity with hysteroscopic biopsy forceps, and B) 38 controls who did not undergo surgical endometrial peeling. All patients underwent a subsequent SEET. Main results and the role of chance In total 104 women were included in the cohort. No differences were found in age, body mass index, baseline FSH, AMH, baseline antral follicle count, previous number of stimulation/IVF cycles, number of embryos transferred, and, embryonic quality among cohorts. Evaluating the endometrium, no differences were observed in the endometrial pattern, however, the endometrial thickness was thicker in group B (8.4±1.5mm vs 9.2±1.3mm, p = 0.02). When analyzing the subsequent SEET cycle, women in group A had higher implantation (51.8% vs 40.6%, p = 0.001) and clinical pregnancy rates (63.5% vs 31.4%, p = 0.009). No difference was found in clinical loss rates (9.4% vs 10.1%, p = 0.06) among cohorts. Of the patients who underwent surgical endometrial peeling, 18.1% (12/66) had the following incidental intraoperative findings: mild intrauterine and/or cervical adhesions (5/66, 0.07%), endometrial polyps (10/66, 15.1%), polypoid endometrium (8/66, 12.1%). 64.3% of the patients with incidental findings became pregnant. Limitations, reasons for caution This study is limited by its retrospective nature. Additionally, in patients with noted uterine pathology, appropriate surgical management was administered in the same setting, this could have biased the results. Future randomized controlled trials are needed. Wider implications of the findings This study continues to support the possible benefit of mechanically peeling the superficial endometrial layer through hysteroscopy to increase implantation rates in women with IF who undergo a SEET. Trial registration number NA

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

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). This retrospective cohort study included women aged ≤ 45years 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). The study included 1335 IVF cycles thatwere stratified according toBMI (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. 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

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. Retrospective cohort study. Single university-affiliated infertility practice. 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 July2021. None. 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). 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). Letrozole and natural FET clinical outcomes were improved compared with programmed FET outcomes.

P-679 Comparison of hormone replacement treatment (HRT) and true-natural cycle (t-NC) protocols for endometrial priming: An analysis of 1,815 warmed blastocyst transfer cycles

Abstract Study question Does the ongoing pregnancy rate (OPR) of HRT with or without GnRH-agonist suppression and t-NC protocols differ in patients undergoing warmed blastocyst transfer? Summary answer HRT, with or without GnRH-agonist suppression, and t-NC protocols are associated with comparable OPRs in patients undergoing warmed blastocyst transfer. What is known already Despite the worldwide increase in frozen embryo transfer cycles, the most optimal protocol for priming of the endometrium is debated. Although HRT offers flexibility, recent evidence points tot-NC being superior to HRT regarding safety, i.e., maternal, obstetric, and neonatal outcomes.However, there are still conflicting data regarding pre-clinical losses and reproductive outcomes when comparing the two protocols. Study design, size, duration In this longitudinal prospective study, 1,815 consecutive patients undergoing 1,815 warmed blastocyst transfer cycles at the Anatolia IVF Centre, Ankara, between 2015-2021, were included. HRT with pituitary suppression was the protocol of choice during 2015- 2017, whereas HRT without suppression and t-NC were more commonly employed during the latter part of the period. Participants/materials, setting, methods All patients with an available day-5/6 vitrified blastocyst(s) were included. Each patient was included only once. The three protocols were t-NC and HRT - with or without suppression. The prerequisites for t-NC was being a local patient with regular menstrual cycles. For t-NC, neither human chorionic gonadotropin (hCG) nor luteal phase support was administered. The primary outcome measure was OPR, defined as pregnancy >12 weeks of gestation. Main results and the role of chance Of the 1,815 cycles,124 were t-NC, 477 were HRT with suppression, and 1,214 were HRT without suppression. For the stimulated cycles leading to FET, no difference was seen among the three groups regarding female age, body mass index, duration of infertility, number of previous embryo transfer attempts, ovarian stimulation protocol, estradiol levels on the day of hCG trigger, number of oocytes retrieved, number of preimplantation genetic testing-aneuploidy, freeze-all cycles and number of embryos transferred. The positive pregnancy test rates of the HRT protocol with or without suppression were higher when compared with that of t-NC (63.7%, 66.6%, and 58.1%,respectively; p = 0.05). The respective figure for clinical pregnancy rates were 56.6%, 60.8% and 55.6% (p = 0.07). However, the pre-clinical (biochemical) loss rates (11.9%, 10.9%, and 4.9%, respectively; p = 0.05), as well as the miscarriage rates (11.9%, 10.9%, and 4.9%, respectively; p = 0.04), were higher in the HRT groups with or without suppression compared to those of t-NC. The OPRs of t-NC, HRT with or without suppression were comparable (53.2%, 45.1%, and 49.0%, respectively; p = 0.73). The protocol for endometrial priming was not an independent predictor of ongoing pregnancy at logistic regression analysis when potential confounders were used as covariates (OR = 0.998; 95%CI 0.669-1.490, p = 0.99). Limitations, reasons for caution The longitudinal study design and the lack of obstetric and perinatal outcome data are limitations. Wider implications of the findings Compared with t-NC, the HRT protocol with/without suppression is associated with higher positive pregnancy test rates albeit increased pre-clinical and clinical loss rates, resulting incomparable OPRs. When compared with t-NC, the HRT protocol could be associated with enhanced endometrial receptivity at the expense of decreased selectivity. Trial registration number not applicable

Black race associated with lower live birth rate in frozen-thawed blastocyst transfer cycles: an analysis of 7,002 Society for Assisted Reproductive Technology frozen-thawed blastocyst transfer cycles

To evaluate if racial/ethnic differences in pregnancy outcomes persisted in frozen-thawed embryo transfer (FET) cycles on a national level. Retrospective cohort study. Clinic-based data. A total of 189,000 Society for Assisted Reproductive Technology FET cycles from 2014-2016 were screened, of which 12,000 cycles had available fresh cycle linkage information and ultimately, because of missing data, 7,002 FET cycles were included. Cycles were stratified by race (White, Black, Asian, and Hispanic). None. The primary outcome was live birth rate. Secondary outcomes were implantation rate, clinical pregnancy rate, multiple pregnancy rate, and clinical loss rate (CLR). Live birth rate was significantly lower in the Black vs. White and Asian, but not Hispanic group. Implantation rate was also significantly lower and CLR higher in the Black group compared with all other groups (all P<.01). Black women had a lower risk of live birth (adjusted risk ratio, 0.82; 95% confidence interval [CI], 0.73-0.92) and a higher risk of clinical loss (adjusted risk ratio, 1.59; 95%CI, 1.28-1.99) compared with White women. There was no significant difference between groups in clinical pregnancy rate or multiple pregnancy rate. When the analysis was limited to preimplantation genetic testing FET cycles, there remained a significantly lower implantation rate in the Black group compared with all other groups (all P<.01). Black race remains an independent predictor of reduced live birth rate in FET cycles, likely because of higher CLR.

DOES A HIGH DOSE PROGESTERONE (P) PROTOCOL IMPROVE PREGNANCY OUTCOMES COMPARED TO A STANDARD DOSE P PROTOCOL IN POOR PROGNOSIS PATIENTS UNDERGOING PROGRAMMED FROZEN-THAWED EMBRYO TRANSFER (FET) CYCLES?

Higher P levels have been associated with improved pregnancy outcomes in FET cycles, likely by supporting the luteal phase, stabilizing the endometrium, and through immunomodulatory effects. High-dose P is theorized to improve pregnancy rates in poor prognosis patients undergoing programmed FET cycles. Our objective is to compare pregnancy outcomes of a standard dose P protocol (75 mg intramuscular [IM] progesterone in oil [PIO]) to outcomes of a high dose P protocol (100 mg IM PIO plus vaginal P) for patients undergoing programmed FET cycles. This was a retrospective cohort study of 348 programmed FET cycles in which at least 1 high quality autologous blastocyst was transferred. Cycles from 2015-2020 in poor-prognosis patients, defined by history of at least 1 prior failed FET, who were aged 18-47 were included. The primary outcome was the ongoing pregnancy rate (OPR), and secondary outcomes included implantation rate (IR), clinical pregnancy rate (CPR), and clinical loss rate (CLR). Analysis was performed in SPSS version 27. Chi-square test was used for categorical data and independent samples T-test for continuous data. A two-sided p-value of <0.05 was considered statistically significant. Patients in the high dose P group were more likely to be nulliparous, had failed more prior FETs, and were more likely to be transferring a euploid embryo. The unadjusted OPR was not different between the two groups, and neither were any of the secondary outcomes (Table 1).Tabled 1Table 1:Characteristic / OutcomeStandard dose P (n = 296)High dose P (n = 52)p valueParous Status (%, n)33.1 (98/296)11.5 (6/52)0.002Number of prior failed FETs (n, mean ± SD)1.1 ± 0.31.6 ± 0.8<0.001Preimplantation genetic testing utilized (%, n)30.7 (91/296)67.3 (35/52)<0.001Implantation rate (%, n)58.6 (226/386)56.1 (37/66)0.71Clinical pregnancy rate (%, n)67.6 (200/296)63.5 (33/52)0.56Ongoing Pregnancy rate (%, n)56.4 (167/296)53.8 (28/52)0.73Clinical loss rate (%, n)17.0 (34/200)15.2 (5/33)0.79 Open table in a new tab In programmed FET cycles, the high dose P protocol yielded similar pregnancy outcomes compared to a standard dose P protocol. While this analysis attempted to match patients for prognosis by history of at least 1 failed FET, the high-dose P group was found to have poorer prognostic characteristics than the standard dose P group.

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

ObjectiveTo compare in vitro fertilization (IVF) outcomes for preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) using various testing platforms.DesignRetrospective cohort.SettingLarge academic IVF center.Patient(s)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.Intervention(s)PGT-SR.Main Outcome Measure(s)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.Result(s)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%).Conclusion(s)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.

PREGNANCY OUTCOMES IN LETROZOLE OVULATION INDUCTION FROZEN-THAWED EMBRYO TRANSFER CYCLES AS COMPARED TO NATURAL AND PROGRAMMED CYCLES

The optimal endometrial preparation for frozen-thawed embryo transfer (FET) cycles is controversial and variable among IVF centers. Our aim is to compare pregnancy outcomes between letrozole ovulation induction FET cycles, natural FET cycles and programmed FET cycles in a US-based population. Single academic center retrospective cohort study. 2310 cycles consisting of patients <43 years utilizing embryos created from autologous oocytes between 2015-2020 were included. Blastocyst embryo transfer occurred 6 days after a natural LH surge to >20 mIU/mL in natural and letrozole cycles, or 6 days after the initiation of intramuscular progesterone in programmed cycles. The primary outcome was the ongoing pregnancy rate (OPR), and secondary outcomes included pregnancy rate (PR), implantation rate (IR), clinical pregnancy rate (CPR), and clinical loss rate (CLR). Chi-square test for categorical data and one-way ANOVA for continuous data was used with Bonferroni correction for multiple comparisons. Multiple logistic regression analysis was performed adjusting for age, BMI, anovulation diagnosis, number of embryos transferred and utilization of preimplantation genetic testing for aneuploidy (PGT-A). A two-sided p-value of <0.05 was considered statistically significant. There was a higher proportion of patients with a diagnosis of anovulation in both letrozole and programmed FET cycles compared with natural cycles (p < 0.01). Patients undergoing programmed FET cycles were more likely to be younger, have a higher BMI, and to have more embryos transferred compared to patients undergoing natural FET and letrozole FET cycles (p < 0.01). The OPRs and CPRs were similar between the groups, while the CLRs were higher in the programmed compared with natural and letrozole FET cycles. After adjusting for potential covariates, the probability of clinical loss was still significantly higher in programmed cycles compared with natural and letrozole FET cycles (aOR 1.58; 95% CI, 1.15-2.12; p < 0.01).Tabled 1OutcomeNatural FET (n = 1135)Letrozole FET (n = 88)Programmed FET (n = 1087)p valuePR (%, n)77.8 (883/1135)78.4 (69/88)79.9 (869/1087)0.46IR (%, n)62.1 (877/1413)63.4 (64/101)62.1 (903/1455)0.96CPR (%, n)68.8 (781/1135)67.0 (59/88)69.5 (755/1087)0.87OPR (%, n)60.4 (686/1135)59.1 (52/88)56.9 (619/1087)0.25CLR (%, n)11.5 (90/781)11.9 (7/59)17.5 (132/755)<0.01 Open table in a new tab Letrozole ovulation induction may be a better alternative to programmed FET cycles particularly for anovulatory patients in view of the lower clinical loss rate.

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

To assess whether GnRH agonist trigger impacts the implantation potential of euploid embryos. 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. 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). Our findings confirm that euploid embryos created after hCG or GnRHa trigger have the same potential for pregnancy.

When next-generation sequencing-based preimplantation genetic testing for aneuploidy (PGT-A) yields an inconclusive report: diagnostic results and clinical outcomes after re biopsy.

To describe diagnostic results following re-biopsy of blastocysts with inconclusive results on preimplantation genetic screening for aneuploidy (PGT-A) and to evaluate the reproductive potential of re-biopsied blastocysts. This retrospective cohort study included all trophectoderm biopsies submitted for PGT-A by a large in vitro fertilization center to a single genetics laboratory from June 2016 to October 2018. PGT-A was performed using next-generation sequencing (NGS). No-result blastocysts that underwent re-biopsy were subsequently classified as euploid, aneuploid, mosaic/segmental, or no-result. Ongoing pregnancy and clinical loss rates were assessed following transfer of re-biopsied blastocysts. Logistic regressions were conducted to account for age and blastocyst morphology. Of the trophectoderm biopsies submitted for PGT-A, 635/25,199 (2.5%) were categorized as no-result. Those that underwent re-biopsy (n = 250) had a 95.2% diagnostic rate with 140 (56.0%) receiving euploid diagnoses. Thirty-six re-biopsied blastocysts deemed euploid were subsequently transferred, resulting in 18 (50.0%) ongoing pregnancies and 5 (13.9%) clinical losses. After adjusting for age and blastocyst morphology, there remained a lower ongoing pregnancy rate and a trend towards higher clinical loss rate following transfer of a re-biopsied blastocyst. When compared to blastocysts that underwent the same number of vitrification-warming cycles but only one biopsy, there were no differences in outcomes. Failure to obtain an analytical result does not change the probability that a given blastocyst is euploid. Pregnancy outcomes following transfer of re-biopsied blastocysts are favorable, but further data must be accrued for an adequately powered comparison with outcomes after transfer of blastocysts biopsied once.

What is the reproductive potential of day 7 euploid embryos?

What is the rate of euploidy and the reproductive potential of embryos biopsied after 6days of development? Embryos biopsied after 6days of development have higher rates of aneuploidy; however, day 7 euploid embryos selected at transfer can achieve acceptable pregnancy rates and live birth (LB) outcomes. Recent publications have shown promising treatment results after euploid day 7 embryo transfers (ETs), albeit these studies were limited by small sample sizes. Whereas the current clinical standard has been to discard embryos that do not reach expansion by day 6 of development, the lack of robust data surrounding the clinical utility of day 7 embryos warrants further evaluation. Retrospective cohort analysis in a single, academic in vitro fertilization (IVF) center from January 2012 to March 2018. A total of 25 775 embryos underwent trophectoderm (TE) biopsy and preimplantation genetic testing for aneuploidy (PGT-A). Additionally, the clinical IVF outcomes of 3824 single, euploid frozen embryo transfer (FET) cycles were evaluated. Cohorts were segregated by day of TE biopsy following oocyte retrieval (day 5, day 6 or day 7). PGT-A was performed to identify embryonic ploidy rates. Secondly, IVF and LB outcomes after single, euploid FET were evaluated for each cohort. A total of day 5 (n= 12 535), day 6 (n= 11 939) and day 7 (n= 1298) embryos were included in the study analysis. The rate of embryo euploidy was significantly lower in day 7 blastocysts compared to day 5 or day 6 cohorts (day 7 = 40.5%; day 5 = 54.7%; day 6 = 52.9%; (P< 0.0001)). After adjusting for age, anti-Müllerian hormone, BMI, embryo quality and number of embryos biopsied, there was a significant association between aneuploidy and embryos biopsied on day 7 when compared to day 5 biopsied embryos (OR = 1.34, CI 95% 1.09-1.45, P= 0.001) and day 6 biopsied embryos (OR = 1.26, CI95% 1.07-1.16, P< 0.001).A sub-analysis of subsequent 3824 single, euploid FET cycles (day 5: n= 2321cycles; day 6: n= 1381cycles; and day 7: n= 116cycles) showed significant differences among cohorts in implantation, clinical pregnancy, LB and clinical loss rates. There was a significant decrease in the odds of implantation, clinical pregnancy and LB, but no association with clinical loss or multiple pregnancy rates in patients who utilized day 7-biopsied embryos during treatment. The retrospective nature of the study and potential variability in the study center's laboratory protocol(s) compared to other reproductive treatment centers may limit the external validity of our findings. Additionally, patients who transferred euploid embryos, biopsied on day 7 of development due to an absence of day 5 or day 6 counterparts, may have introduced selection bias in this study. Embryonic developmental stage, morphological grade and ploidy status are paramount factors affecting ET selection and implantation potential. This study reveals that embryos ineligible for TE biopsy on day 5 or day 6 of development may benefit from extended culture to day 7. Our study demonstrates patient benefit when extended culture to day 7 of development is routinely performed for embryos failing to meet biopsy criteria by day 5 or 6. No funding was received for the realization of this manuscript. Dr Alan Copperman is Advisor or Board Member of Sema 4 (Stake holder in Data), Progyny and Celmatix. This retrospective analysis was approved by an Institutional Review Board (WIRB PRO NUM: 20161791; Study Number: 1167398).

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

It is now well known that GnRH agonist (GnRHa) when used to trigger final oocyte maturation results in early luteolysis and consequently luteal phase dysfunction in fresh autologous IVF cycles. However, with the use of adjuvant low dose hCG, pregnancy outcomes are favorable and comparable to after hCG trigger(1). This suggests that GnRHa trigger does not impact oocyte or embryo quality. Furthermore, previous studies have shown comparable live birth rates after frozen-thawed embryo transfer (FET) cycles utilizing embryos obtained from cycles triggered previously with GnRHa versus hCG (2). Previous studies have also shown comparable euploid rates after GnRHa and hCG trigger (3). However, there are no studies evaluating pregnancy rates after transfer of euploid frozen embryos derived from cycles triggered with either GnRHa or hCG trigger. To compare pregnancy outcomes for frozen-thawed single euploid embryo transfer cycles that were generated from cycles triggered with either GnRHa or hCG. Retrospective cohort study done at a single academic IVF center evaluating frozen-thawed embryo transfer (FET) cycles in which single euploid blastocysts were transferred over a four year period. All embryos were generated in preceding fresh autologous IVF cycle in which hCG or GnRHa was used for final oocyte maturation. Embryos were subsequently transferred in a medicated or natural frozen cycle (44.3% medicated cycles in hCG group v. 37.0% in GnRHa group, p>0.05.) Patients were excluded if they had >1 embryo transferred, day 3 embryo biopsies, donor oocyte cycles or dual trigger with both hCG and GnRHa. Primary outcome was ongoing pregnancy rate or live birth rate (OPR/LBR) Secondary outcomes were clinical pregnancy rate (CPR), clinical loss rate (CLR) and multiple pregnancy rate (MPR.) Student’s t-test was used to analyze continuous variables and Chi Square test was used for categorical variables. Multivariate logistical regression was performed to control for potential confounding variables. A p-value of <0.05 was considered statistically significant. A total of 215 FET cycles were included for analysis (hCG trigger, n=115 subjects; GnRHa trigger, n=100 subjects.) The GnRHa group was significantly younger (34.8 years old v. 37.2 years old) and had higher baseline AMH values (4.55 ng/ml versus 2.1 ng/ml) than the hCG group, respectively (p<0.05.) There was no significant difference in OPR/LBR (60.9% v. 62.0%), CPR (68.7% v. 69.0%), CLR (8.9% v. 10.1%) or MPR (1.3% v. 2.9%) in the GnRHa v. hCG groups, respectively. Using logistic regression to control for the significant confounding variables of age and AMH value, the adjusted odds ratio for live birth was 1.09 (95% CI 0.60-1.99, p=0.77) when GnRHa trigger was compared to hCG trigger.Table 1Pregnancy Outcomes After Single Euploid Embryo Transfer in FET cycles Triggered by hCG or GnRHa Stratified by AgeAge Group<35 YO>35 YOAll PatientsPregnancy OutcomehCG (n=29)GnRHa (n=55)hCG (n=86)GnRHa (n=45)hCG (n=115)GnRHa (n=100)IR20/29 (69.0%)41/55 (74.5%)60/86 (69.8%)29/45 (64.4%)80/115 (69.6%)70/100 (70.0%)CPR19/29 (65.5%)41/55 (74.5%)60/86 (69.8%)28/45 (62.2%)79/115 (68.7%)69/100 (69.0%)OPR/LBR16/19 (55.2%)36/55 (65.5%)54/86 (62.8%)26/45 (57.8%)70/115 (60.9%)62/100 (62.0%)CLR3/19 (15.8%)5/41 (12.2%)6/60 (10.0%)2/28 (7.1%)9/79 (8.9%)7/69 (10.1%)MPR1/19 (5.3%)1/41 (2.4%)0/60 (0.0%)1/28 (3.6%)1/79 (1.3%)2/69 (2.9%)∗ There were no significant differences in any of the variables listed above (p>0.05) Open table in a new tab ∗ There were no significant differences in any of the variables listed above (p>0.05) Our findings confirm that euploid embryos created after hCG or GnRHa trigger have the same potential for pregnancy.

T-shaped uterine cavity morphology as assessed by three-dimensional ultrasound (3D US) is associated with lower sustained implantation rates and higher clinical loss rates following frozen embryo transfer

T-shaped uterine cavity morphology as assessed by three-dimensional ultrasound (3D US) is associated with lower sustained implantation rates and higher clinical loss rates following frozen embryo transfer

Pregnancy outcomes between euploid and non-tested blastocysts in frozen embryo transfer cycles

Debate continues on the clinical value of preimplantation genetic screening (PGS) and whom it may benefit. We compared pregnancy outcomes in frozen embryo transfer (FET) cycles between non-tested blastocyst transfers immediately following a freeze-all in vitro fertilization (IVF) cycle and euploid blastocyst FET cycles. Retrospective cohort study. 279 cycles performed at a large university-based center during a four-year period were evaluated. 116 blastocyst FET cycles subsequently following a freeze-all IVF cycle and 163 euploid blastocyst FET cycles were included for analysis. The primary outcome was ongoing pregnancy rate (OPR). Secondary outcomes included implantation rate (IR), clinical pregnancy rate (CPR), clinical loss rate (CLR) and multiple pregnancy rate (MPR). Patients were further stratified by age and number of embryos transferred. Student’s t-test was used to assess continuous variables. Chi-square and Fisher’s exact test was used to assess categorical variables. Multivariate logistical regression was performed to control for potential confounding variables. A p-value <0.05 was considered statistically significant. Among all patients, IR (67.2% vs. 71.5%, p=0.45), CPR (76.7% vs. 72.4%, p=0.42), OPR (61.2% vs. 63.8%, p=0.66) and CLR (20.2% vs. 11.8%, p=0.09) were similar between the two groups. Those in the non-tested FET group demonstrated an increased MPR (29.2% vs. 16.2%, p=0.02); however, this was no longer appreciated in patients receiving a single embryo transfer (2.5% vs 3.4%, p = 0.80). Outcomes were stratified by age (Table). Using logistic regression to control for significant confounding variables of age, BMI, and endometrial preparation protocol, the adjusted odds ratio for OPR was 0.77 (95% CI 0.46-1.30, p=0.33). PGS improves pregnancy and clinical loss rates in an older patient population. Women under 35 years utilizing PGS had decreased multiple pregnancy rates; however, if a single blastocyst transfer was performed there was no benefit to testing embryos.Tabled 1Pregnancy Outcomes Stratifed by AgeIR, n (%)CPR, n (%)OPR, n (%)CLR, n (%)MPR, n (%)<35 PGS62/85 (72.9)55/75 (73.3)46/75 (61.3)9/55 (16.3)5/55 (9.1)<35 Untested79/104 (76.0)62/75 (82.7)54/75 (72.0)7/62 (11.2)17/62 (27.4)36-37 PGS30/44 (68.2)25/36 (69.4)24/36 (66.7)1/25 (4.0)4/25 (16.0)36-37 Untested21/40 (52.5)13/23 (56.5)10/23 (43.5)3/13 (23.1)6/13 (46.2)38-40 PGS37/45 (82.2)26/32 (81.3)25/32 (78.1)1/26 (3.8)10/26 (38.5)38-40 Untested13/21 (61.9)11/12 (91.7)7/12 (58.3)4/11 (36.3)3/11 (27.3)41-42 PGS10/16 (62.5)10/14 (71.4)7/14 (50.0)3/10 (30.0)0/10 (0.0)41-42 Untested3/10 (30.0)3/5 (60.0)0/5 (0.0)3/3 (0.0)0/3 (0.0)Bold: p<0.05 Open table in a new tab

Are pregnancy rates affected by day of blastocyst cryopreservation in single euploid frozen embryo transfer cycles?

There is inconclusive evidence whether day of cryopreservation of euploid embryos affects pregnancy rates. We sought to compare pregnancy outcomes between euploid blastocyst embryos cryopreserved on either day 5 or 6. Retrospective cohort study. 126 cycles performed at a large university-based center during a period of January 2013 through December 2016 were evaluated. Euploid embryos cryopreserved on either day 5 (n=77) or day 6 (n=51) and utilized in a single frozen embryo transfer (FET) cycle were included for analysis. Preimplantation genetic screening was performed by either array Comparative Genomic Hybridization or Next-Generation Sequencing. Only high quality blastocyst embryos were biopsied and frozen. The primary outcome was ongoing pregnancy rate (OPR). Secondary outcomes included implantation rate (IR), clinical pregnancy rate (CPR), clinical loss rate (CLR) and multiple gestation rate (MGR). Student’s t-test and Mann-Whitney test were used to assess continuous variables depending on how the data was distributed. Chi-square was used to assess categorical variables. Multivariate logistical regression was performed to control for potential confounding variables. A p-value <0.05 was considered statistically significant. No significant differences were noted between the groups for age (35.5±4.3 vs. 35.5±4.0), BMI (25.8±5.8 vs. 25.2±4.6), AMH level (3.1±2.3 vs. 3.6±4.4), previous live birth (37.7% vs. 49.0%), diagnosis of recurrent pregnancy loss (RPL) (23% vs. 14%) and number of prior FET cycles (0.3±0.7 vs. 0.6±0.9). There were no differences in pregnancy outcomes between the two groups (Table). Using bivariate analysis there was no difference in OPR between the two groups (OR: 0.84, 95% CI 0.40 - 1.73, p=0.63). A multivariate regression analysis was performed to control for the potential confounding variables of age, BMI, previous live birth, diagnosis of RPL, or prior FET resulting in an adjusted odds ratio for OPR of 0.78 (95% CI 0.37 - 1.65, p=0.51). Day of cryopreservation does not affect pregnancy outcomes in single euploid blastocyst transfers. Rate of multiples remains low in single embryo transfer cycles.Tabled 1Pregnancy OutcomesDay 5Day 6p-valueIR, n (%)55/77 (71.4)36/51 (70.6)nsCPR, n (%)53/77 (68.8)35/51 (68.6)nsOPR, n (%)45/77 (58.4)32/51 (62.7)nsCLR, n (%)8/53 (15.1)3/35 (8.6)nsMGR, n (%)1/53 (1.9)2/35 (5.7)nsns=not significant Open table in a new tab

The effect of ICSI, maternal age, and embryonic stage on early clinical loss rate of twin versus singleton pregnancies

Objectives To compare early loss rates between twin and singleton pregnancies following ART. Study design First-trimester sonography counted the number of embryos with positive heartbeat in women undergoing IVF/ICSI and transfer of one to three embryos. The number of lost pregnancies was calculated from a second-trimester sonogram. Loss rates of the entire pregnancy were related to maternal age <38 or ≥38 years, IVF or ICSI, and cleavage or blastocyst stage embryo transfers (in ICSI cases). Results Patients underwent IVF with ( n = 672) and without ( n = 189) ICSI. The overall odds of miscarrying the entire singleton pregnancy were 2.6 times that of a twin gestation (95% CI 1.5, 4.5). The disadvantage for singletons compared to twins seems more apparent in pregnancy after ICSI in the subgroup of patients <38 years (OR 2.9, 95% CI 1.5, 5.8). In this subgroup, the disadvantage conferred to singletons appeared only among days 2–3 embryo transfers (OR 3.0, 95% CI 1.3, 7.2). Conclusion A significantly lower early spontaneous loss rate of twin pregnancies seems related to ICSI followed by cleavage stage embryo transfer in patients <38 years.

Scientific aspects of preconception gender selection

Although numerous methods have been promoted as having an influence on the gender of offspring, most lack credible scientific evidence of effectiveness. Preconception gender selection has an important application in reducing the risk of having children with X-linked disease. A preconception, flow cytometric sperm sorting method of gender selection (MicroSort®) is based upon the detection of differential fluorescence emitted by fluorescently stained X and Y chromosome-bearing spermatozoa. Ongoing clinical trial results illustrate the safety and efficacy of the method. Fluorescence in-situ hybridization (FISH) analysis of specimens pre- and post-sort show the 50:50 X:Y ratio in unsorted spermatozoa can be shifted to 90% X or 75% Y after sorting. Embryo gender and fetal/baby gender are consistent with post-sort FISH results. Intrauterine insemination (IUI) and IVF/ICSI (intracytoplasmic sperm injection) pregnancy rates are consistent with those reported in the assisted reproduction literature. Clinical loss rates are similar to those in the general population. The observed major congenital abnormality rate of 2.05% for babies born after using this sperm sorting method coincides with that occurring spontaneously. Current results indicate that the method is a safe and effective process and is a valuable tool for families wishing to balance the gender distribution of their children or to reduce the likelihood of having children with X-linked disease.

What is a preclinical pregnancy loss?

To evaluate the contribution of embryo quality to preclinical loss rates after in vitro fertilization (IVF)/embryo transfer (ET) pregnancy, multiple gestation, and clinical loss rates were compared to preclinical pregnancy loss rates over a 3-year period. The pregnancy outcomes after 1675 fresh ETs from 1994 to 1997 were studied. While establishment of a clinical pregnancy confirms uterine receptivity, multiple gestation rates reflect embryo quality. Because the majority of clinical losses are chromosomally abnormal, clinical loss rates serve as another indicator of embryo quality. The overall preclinical pregnancy loss rate was 5% (78/1675) of ETs and 17% (78/472) of pregnancies. During the 3-year period the pregnancy rates per ET increased from 19 to 36% (P < 0.0001), multiple gestation rates increased from 21 to 48% (P < 0.008), clinical loss rates decreased from 20 to 6% (P < 0.0001), and preclinical pregnancy loss rates remained unchanged from 13 to 19% (P = 0.1). Preclinical pregnancy loss more likely reflects abnormalities in uterine receptivity rather than embryo quality. If recurrent preclinical pregnancy loss occurs after IVF/ET, evaluation for abnormalities of uterine receptivity should be performed.