Single Embryo Transfer Research Articles

The Efficacy of Letrozole Co-Treatment in an Antagonist Protocol for Women with Polycystic Ovary Syndrome Undergoing IVF: A Retrospective Study.

Our objective was to investigate the efficacy of letrozole co-treatment in an antagonist protocol for infertile women with polycystic ovary syndrome (PCOS). This retrospective cohort study included infertile women with PCOS undergoing IVF/ICSI with and without letrozole co-treatment in an antagonist protocol from 2007-2021 at Shanghai Ninth People's Hospital (Shanghai, China). A total of 1559 participants were enrolled, with 1227 women in the antagonist group and 332 women in the letrozole co-treatment group. Propensity score-based patient-matching model was conducted to balance covariates between the groups. The primary outcome was the number of retrieved oocytes, with secondary outcomes including endocrine parameters, ovarian stimulation outcomes, pregnancy outcomes, and obstetrical and neonatal complications. Letrozole co-treatment induced significant changes in hormonal regulation, increased the percentage of large follicles, and resulted in fewer retrieved oocytes (P < 0.05). However, there was no negative impact on the number of usable embryos or good-quality embryos (P > 0.05). The live birth rates following fresh embryo transfer were comparable between the letrozole and control groups (single embryo transfer: 28.9% vs 29.7%, P > 0.05; double embryo transfer: 37.3% vs 45.6%, P > 0.05). Additionally, there were no significant differences between the two groups in the live birth rate per patient after frozen embryo transfer and the cumulative live birth rate (P > 0.05). No significant differences in obstetrical and neonatal complications were observed between the groups (P > 0.05). The addition of letrozole to the antagonist protocol for women with PCOS undergoing IVF induces a higher percentage of large follicles during oocyte retrieval, while reducing the overall number of retrieved oocytes. Moreover, the use of letrozole demonstrates comparable clinical outcomes following embryo transfers. These findings highlight the potential application of letrozole in an antagonist protocol for women with PCOS.

Trends and outcomes of fresh and frozen donor oocyte cycles in the United States

ObjectiveTo examine trends, characteristics, and outcomes of donor oocyte embryo transfer cycles by original oocyte and resultant embryo state and determine whether oocyte state (fresh or frozen) is differentially associated with clinical pregnancy, live birth, and term, normal birthweight neonates among singleton live births. DesignRetrospective cohort study SubjectsPatients undergoing donor oocyte embryo transfer cycles in the United States reporting to National Assisted Reproductive Technology Surveillance System (NASS) from 2013–2020 ExposureOriginal donor oocyte and resultant embryo state (fresh or frozen) Main Outcome MeasuresAnnual numbers and proportions of total donor oocyte embryo transfer cycles stratified by oocyte and embryo state and single embryo transfer cycles resulting in live birth of term (≥37 weeks gestation), normal birthweight (≥2500g) singletons during 2013–2020. Rates of live birth and term, normal birthweight neonates among singleton live births for 2018–2020 are also reported. Relative risks (RR) examine associations between donor oocyte state and live birth and term, normal birthweight neonates among singleton live births resulting from donor oocyte embryo transfer cycles. ResultsFrom 2013-2020, there were 135,085 donor oocyte embryo transfer cycles, of which the proportions increased for frozen embryos (42.3% to 76.6%), fresh embryos using frozen donor oocytes (19.9% to 68.3%) and single embryo transfer (SET) (36.4% to 85.5%). During 2018–2020, there were 48,679 donor oocyte embryo transfer cycles. Rates of live birth were lower with frozen compared to fresh donor oocytes for both fresh (46.2%, 55.9%; aRR 0.83 [95% CI 0.79–0.87]) and frozen (41.3%, 45.8%; aRR 0.94 [95% CI 0.91–0.98]) embryo transfer cycles. Among singleton live births, rates of delivering a term, normal birthweight neonate were similar for frozen compared to fresh donor oocyte transfer cycles among fresh (77.3, 77.2%; aRR 1.01 [95% CI 0.98–1.03]) and frozen (75.6, 75.1%; aRR 1.02 [95% CI 0.99–1.04]) embryos. ConclusionIn this national study of donor oocyte embryo transfer cycles, frozen embryo transfers, fresh embryo transfers using frozen oocytes, and SET increased. Although frozen compared to fresh oocytes were associated with a slightly reduced rate of live birth, rates of term, normal birthweight neonates among singleton live births were comparable between donor oocyte states.

International Committee for Monitoring Assisted Reproductive Technology world report: assisted reproductive technology, 2015 and 2016

ObjectiveTo report utilization, effectiveness, and safety of assisted reproductive technologies in 2015 and 2016. DesignRetrospective, cross-sectional survey of 3103 assisted reproductive technology clinics in 74 countries in 2015 and 3249 clinics in 79 countries in 2016 that submitted cycle and pregnancy outcome data through national and regional registries. SubjectsPatients undergoing assisted reproductive technology procedures. ExposureAssisted reproductive technology. Main Outcome MeasuresOutcomes on country, regional, and global levels. ResultsReported for 2015: 2,358,239 cycles with 548,652 babies born; for 2016: 2,807,963 cycles with 647,188 babies born. Estimated in 2015, ≥2,683,677 cycles resulted in >675,134 babies; in 2016, ≥3,100,448 cycles resulted in ≥723,026 babies. Reported cycles represent approximately 80% of global utilization. In 2015 and 2016, 27.6% and 27.8%, respectively, of women undergoing fresh autologous cycles were age ≥40 years. Frozen-thawed embryo transfer cycles accounted for 47.0% and 51.9%, respectively, of all embryo transfers in 2015 and 2016. Oocyte donation cycles accounted for 6.7% and 7.1% of all embryo transfers in 2015 and 2016. Intracytoplasmic sperm injection was performed in 57.7% and 56.4% of autologous aspiration cycles in 2015 and 2016, respectively. The cumulative delivery rate per aspiration cycle for fresh and frozen-thawed embryo transfer was 32.4% in 2015 and 33.1% in 2016, respectively. The average number of transferred embryos was 1.70 in 2015 and 1.69 in 2016. The proportion of single embryo transfers in fresh autologous cycles increased from 42.1% in 2015 to 44.0% in 2016. The twin delivery rate decreased from 16.0% in 2015 to 14.7% in 2016, and the triplet rate decreased from 0.6% in 2015 to 0.4% in 2016. The proportion of single embryo transfers in frozen-thawed embryo transfer autologous cycles was 62.2% in 2015 and 64.2% in 2016, with twin and triplet rates of 10.1% and 0.3% in 2015 and 10.0% and 0.2% in 2016, respectively. ConclusionUtilization of assisted reproductive technology and births per cycle increased from 2015 to 2016 while multiple births were reduced . Increasing proportion of frozen-thawed embryo transfer cycles, continuing wide variation in use of intracytoplasmic sperm injection, and increase in single embryo transfer rates are reported.

Racial disparities in the outcomes of euploid single frozen-thawed embryo transfer cycles – analysis of the Clinical Outcome Reporting System of the Society for Assisted Reproductive Technology 2016–2018 data

ObjectiveTo evaluate if in pregnancies conceived with the transfer of single genetically tested embryos, maternal race and ethnicity relate to pregnancy outcome. DesignRetrospective cohort. SubjectsAutologous frozen -thaw embryo transfer (FET) cycles with transfer of single genetically tested embryo in SART-CORS for years 2016-2018; cycles associated with diagnoses of recurrent pregnancy loss, gestational carrier, donor egg and donor embryo were excluded. ExposureInformation on race and ethnicity linked with in vitro fertilization and FET cycles available in the SART-CORS. Main Outcome MeasuresMultivariable analyses utilizing generalized estimating equation examined the relationship between categories of race and ethnicity with the following outcomes: Pregnancy (+βhCG following FET), clinical pregnancy, pregnancy loss (early [at gestation <13 weeks] and late [loss between ≥13 and <20 weeks]), preterm (<37 weeks), term (≥37 weeks) and live birth. Covariates adjusted for included age, BMI, AMH, infertility diagnosis and smoking history. Results79,416 FET cycles met the eligibility criteria. Information on race and ethnicity was specified for 50,820 (64.0%) and was not known in 28, 723 (36%) of the cycles . The population was predominantly non-Hispanic White (NHW, 44%). Non-Hispanic Black [NHB] comprised 2.7%, Asian 12.3%, Hispanic 3.4%, American Indian, Pacific Islander, Hawaiian and Alaskan [AI_AL_PI_H] 0.2%. Nearly 1.0 % self-identified with more than one race. On multivariable analyses, pregnancies in NHB and in Hispanic women (compared to NHWs) were significantly more likely to result in in preterm birth (p<0.001). Compared to NHW women, the likelihood of live birth was significantly lower in NHBs (p<0.01), Asian (p=0.04), Hispanic (<0.01) and AI_AL_PI_H women (p<0.01). . The likelihood for delivery by Cesarean was also disproportionately higher in the NHB (p=0.047), Hispanic (p=0.007) and in women identifying with more than one race (0.023)compared to NHWs . ConclusionRacial and ethnic differentials are apparent in the outcomes of FET conceived pregnancies resulting from the transfer of single genetically tested embryos.

Undisturbed culture: a clinical examination of this culture strategy on embryo in vitro development and clinical outcomes

To compare the effect of a fully undisturbed culture strategy over a sequential one on embryo in vitro development and clinical outcomes in ICSI cycles. Retrospective cohort study. This study included 4,564 ICSI cycles performed over 5 years, including autologous and oocyte donation treatments with extended embryo culture until blastocyst in one of the two defined culture strategies. Embryo cohorts were cultured in one of two culture systems: a fully undisturbed culture, including an incubator with integrated time-lapse technology, one-step culture medium and embryo selection assisted by semi-automatic tools based on embryo morphokinetics, or a sequential culture, using a conventional benchtop incubator, sequential media and traditional morphological evaluation under optical microscope. The effect of the culture strategies over embryo development and clinical outcomes was quantified by generalized estimated equations, controlling for possible confounders through the inverse probability of treatment weighting method. Weighted odds ratios (OR) and 95% confidence intervals (CI) for live birth rate after fresh single embryo transfer and the cumulative live birth rate. Additionally, blastocyst development and morphology and other intermediate outcomes were also assessed. A significant positive association was found between the employment of undisturbed embryo culture and higher live birth rate in the first embryo transfer in both autologous (OR=1.617, 95%CI: 1.074-2.435) and oocyte donation cycles (OR=1.316, 95%CI: 1.036-1.672). Cumulative live birth rate after one year follow-up was also positively associated with the undisturbed culture strategy in oocyte donation cycles (OR=1.5, 95%CI: 1.179-1.909), but not in autologous cycles (OR=1.051, 95%CI: 0.777-1.423). Similarly, blastocyst rate, good morphology blastocyst rate and utilisation rate were positively associated with the employment of undisturbed culture in oocyte donation cycles, but not in autologous cycles. These findings imply that a culture system combining integrated time-lapse incubators with a one-step culture medium, may enhance the success rates of patients undergoing ICSI treatment by increasing the production of higher-quality blastocysts and improving embryo selection while streamlining laboratory procedures and workflow.

A modified flexible GnRH antagonist protocol using antagonist early cessation and a gonadotropin step-down approach improves live birth rates in fresh cycles: a randomized controlled trial.

Can pregnancy outcomes following fresh elective single embryo transfer (eSET) in gonadotropin-releasing hormone (GnRH) antagonist protocols increase using a gonadotropin (Gn) step-down approach with cessation of GnRH antagonist on the day of hCG administration (hCG day) in patients with normal ovarian response? The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on the hCG day is effective in improving live birth rates (LBRs) per fresh eSET cycle. Currently, there is no consensus on optimal GnRH antagonist regimens. Studies have shown that fresh GnRH antagonist cycles result in poorer pregnancy outcomes than the long GnRH agonist (GnRHa) protocol. Endometrial receptivity is a key factor that contributes to this phenomenon. An open label randomized controlled trial (RCT) was performed between November 2021 and August 2022. There were 546 patients allocated to either the modified GnRH antagonist or the conventional antagonist protocol at a 1:1 ratio. Both IVF and ICSI cycles were included, and the sperm samples used were either fresh or frozen from the partner, or from frozen donor ejaculates. The primary outcome was the LBRs per fresh SET cycle. Secondary outcomes included rates of implantation, clinical and ongoing pregnancy, miscarriage, and ovarian hyperstimulation syndrome (OHSS), as well as clinical outcomes of ovarian stimulation. Baseline demographic features were not significantly different between the two ovarian stimulation groups. However, in the intention-to-treat (ITT) population, the LBRs in the modified antagonist group were significantly higher than in the conventional group (38.1% [104/273] vs. 27.5% [75/273], relative risk 1.39 [95% CI, 1.09-1.77], P = 0.008). Using a per-protocol (PP) analysis which included all the patients who received an embryo transfer, the LBRs in the modified antagonist group were also significantly higher than in the conventional group (48.6% [103/212] vs. 36.8% [74/201], relative risk 1.32 [95% CI, 1.05-1.66], P = 0.016). The modified antagonist group achieved significantly higher implantation rates, and clinical and ongoing pregnancy rates than the conventional group in both the ITT and PP analyses (P < 0.05). The two groups did not show significant differences between the number of oocytes retrieved or mature oocytes, two-pronuclear zygote (2PN) rates, the number of embryos obtained, blastocyst progression and good-quality embryo rates, early miscarriage rates, or OHSS incidence rates (P > 0.05). A limitation of our study was that the subjects were not blinded to the treatment allocation in the RCT trial. Only women under 40 years of age who had a good prognosis were included in the analysis. Therefore, use of the modified antagonist protocol in older patients with a low ovarian reserve remains to be investigated. In addition, the sample size for Day 5 elective SET was small, so larger trials will be required to strengthen these findings. The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on hCG day improved the LBRs per fresh eSET cycle in normal responders. This project was funded by grant 2022YFC2702503 from the National Key Research & Development Program of China and grant 2021140 from the Beijing Health Promotion Association. The authors declare no conflicts of interest. The RCT was registered in the Chinese Clinical Trial Registry; Study Number: ChiCTR2100053453. 21 November 2021. 23 November 2021.

Diameter of Human Day Five Blastocysts and Birth Sex.

Background This study aimed to evaluate the offspring sex ratio, born through fresh and cryo-thawed single blastocyst (BL) transfers regarding a single morphological, static parameter, namely, BL diameter. Methodology This retrospective, observational study was conducted at an assisted reproductive technology (ART) center, Kinderwunschzentrum Niederrhein Germany. We conducted a statistical analysis of all births resulting from fresh and thawed in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles after a single embryo transfer (SET). The main outcome measure was the offspring sex ratio after SET of a day five BL in relation to the BL diameter measurement. Results There were more female than male babies born in our study. We observed a tendency for BL to have a higher diameter, resulting in female offspring, which was not statistically relevant. We also compared the BL diameter in the fresh embryo transfer (ET) group with that of the cryo-thawed ET group, showing a tendency toward a larger diameter in the fresh ET group. In the ICSI cycles, there was a higher tendency for a larger BL diameter when compared to IVF cycles. In the fresh ET cycles, BL leading to the male sex at birth had a tendency toward a larger diameter than the female BL. In the cryo-thaw ET cycles, BL leading to the female sex had a tendency toward a larger diameter than the male BL. Conclusions Our results showed a tendency in the sex of offspring toward the female sex and no significant difference in the BL diameter of BL leading to birth after ART and consecutive transfer of day five BL.

Relationship between fresh single embryo morphology scores and serum HCG values at 14 days and 14–18-day doubling values

Research questionWhat is the effect of embryo morphology score on 14-day β-HCG levels and 14–18-day β-HCG doubling values, and do they have differences in day-3 embryo or day-5 blastocyst transfers? DesignRetrospective analysis of 4434 fresh cycles of single embryo transfers (SET) with β-HCG ≥15 mIU/ml on day 14 after transfer via IVF and ICSI. The correlation between embryo morphology score and 14-day β-HCG was examined. Doubling of 14–18 day β-HCG was analysed in 2628 cycles to determine correlations with embryo morphology score. ResultsIn day-3 SET, number of embryonic cells was positively correlated with 14-day post-transfer β-HCG values (R = 0.076; P = 0.013). No significant correlation was observed between the grade of the transferred embryos and the 14–18-day serum β-HCG doubling values. In day-5 single blastocyst transfers, the degree of blastocyst expansion, trophoblast cell and inner cell mass (ICM) grades demonstrated a significant positive correlation with 14-day post-transfer β-HCG (P < 0.001, P = 0.014, P = 0.003). Degree of blastocyst expansion was significantly correlated with 14–18-day β-HCG doubling values (R = –0.051, P = 0.027). Grades of the ICM and trophoblast cells showed no significant correlation with 14–18-day β-HCG doubling values. ConclusionIn fresh SET, embryo morphology score influences 14-day β-HCG values in day-3 embryos and day-5 blastocyst transfers. Embryo morphology score in day-3 SET does not affect 14–18-day β-HCG doubling values. Degree of blastocyst expansion significantly affects 14–18-day β-HCG doubling values in day-5 blastocyst transfers.

Single day 14 serum hCG values allow prediction of viable pregnancy and are significantly higher in frozen as compared to fresh single blastocyst transfer

PurposeTo evaluate if single serum human chorionic gonadotropin (hCG) level measurements are sufficient for pregnancy monitoring after single embryo transfer (sET) and to compare the hCG levels between fresh (FRET) and frozen embryo transfers (FET) in medically assisted reproduction.MethodsThis was a retrospective exploratory cohort study including all patients who met the inclusion criteria, who received a single FRET (n = 249) or FET (n = 410) of a day five blastocyst at the IVF clinic at the Johannes Kepler University Linz between 2011 and 2020. hCG levels were measured on day 14 after embryo transfer. Threshold values for the viability of pregnancies were determined using receiver operating characteristic (ROC) curves.ResultsSignificantly higher hCG levels were found in those who received FET than in those who received FRET (1222.8 ± 946.7 mU/ml vs. 862.7 ± 572.9 mU/ml; p < 0.001). Optimal threshold values predicting a viable pregnancy were 368.5 mU/ml and 523 mU/ml in the FRET and FET groups, respectively.ConclusionsAfter FET, higher hCG values after 14 days of embryo transfer must be considered in pregnancy monitoring. Additionally, a single threshold hCG value seems to be sufficient for determining pregnancy viability. To exclude ectopic pregnancies, subsequent ultrasound examination is a mandatory requirement.

Maternal age at transfer following autologous oocyte cryopreservation is not associated with live birth rates.

Our aim was to evaluate if maternal age at transfer following autologous oocyte cryopreservation is associated with live birth rate (LBR). We performed a retrospective cohort study of all patients who thawed autologous oocytes and then underwent a single frozen euploid embryo transfer between 2011 and 2021 at a large urban university-affiliated fertility center. Each oocyte thaw patient was matched 2:1 to in vitro fertilization (IVF) patients who underwent single embryo transfer < 1year after retrieval. Primary outcome was LBR. Secondary outcomes included implantation rates (IR) and spontaneous abortion rates (SABR). A total of 169 oocyte thaw patients were matched to 338 IVF patients. As expected, oocyte thaw patients were older (median age 42.5 vs. 37.6years, p < 0.001) and waited longer between retrieval and transfer than in vitro fertilization patients (median time 59 vs. 1month, p < 0.001). In univariate analysis, implantation and LBR differed among oocyte thaw and IVF patients (p < 0.05), but SABR did not (p = 0.57). Transfer outcomes in oocyte thaw patients did not differ based on transfer age group (IR: p = 0.18; SABR: p = 0.12; LBR: p = 0.24). In a multiple logistic regression model, age at transfer was not predictive of live birth when controlling for age at retrieval, embryo morphology, and day of blastulation. Maternal age at transfer after oocyte cryopreservation is not predictive of LBR; this suggests that "an aging womb" does not impair LBR after oocyte thaw and empowers patients to return for transfer when ready for childbearing.

Are there associations between clinical and embryological factors with pregnancy loss following transfer of a single euploid embryo?

First trimester pregnancy losses are commonly attributed to chromosomal abnormalities. The causes of pregnancy loss following transfer of a euploid embryo are not fully elucidated. The aim of this study was to evaluate clinical and embryological parameters for pregnancy failure following the transfer of a single euploid embryo. Pregnancy outcomes of single euploid embryo transfers from a single centre between January 2017 and March 2020 were retrospectively evaluated. Several clinical and embryological parameters were evaluated in consideration to pregnancy outcomes; total pregnancy loss and live birth. Endometrial preparation type, number of previous frozen embryo transfer cycles, history of recurrent pregnancy loss, higher body mass index, presence of endometriosis and/or adenomyosis and embryo quality were found to be significantly different between two groups. Morphokinetic parameter analysis of 523 euploid embryos using time-lapse imaging did not show any statistical differences between the two groups, however a significantly higher rate of uneven blastomeres in the cleavage stage was observed in the total preganncy loss group. Evaluation of clinical and embryological data can reveal possible factors associated with pregnancy loss that can facilitate improved patient consultation. Feasible interventions can potentially increase the chance of achieving a live birth.

What is the optimal number of embryos to transfer for POSEIDON group 1 and group 2? A retrospective study

BackgroundThe 2016 Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria redefined the poor responders as low prognosis patients. The embryo transfer strategy for POSEIDON patients remained to be addressed. This study aimed to investigate the optimized number of embryos to transfer for unexpected low-prognosis patients (POSEIDON Group 1 and Group 2) with blastocyst transfer in their first frozen cycle.MethodsA retrospective cohort study of 2970 patients who underwent frozen-thawed embryo transfer (FET) between January 2018 and December 2021. Patients from POSEIDON Group 1 (N = 219) and Group 2 (N = 135) who underwent blastocyst transfer in their first FET cycles were included and divided into the elective single embryo transfer (eSET) group and the double embryo transfer (DET) group.ResultsFor POSEIDON Group 1, the live birth rate per embryo transfer of the DET group was slightly higher than the eSET group (52.17% vs 46.15%, OR 0.786, 95% CI 0.462–1.337, P = 0.374; adjusted OR (aOR) 0.622, 95% CI 0.340–1.140, P = 0.124), while a significant increase of 20.00% in the multiple birth rate was shown. For Group 2, higher live birth rates were observed in the DET group compared to the eSET group (38.46% vs 20.48%, OR 0.412, 95% CI 0.190–0.892, P = 0.024; aOR 0.358, 95% CI 0.155–0.828, P = 0.016). The difference in the multiple birth rate was 20.00% without statistical significance. Univariate and multivariate analyses revealed that age (OR 0.759, 95% CI .624–0.922, P = 0.006 and OR 0.751, 95% CI 0.605–0.932, P = 0.009) and the number of transferred embryos (OR 0.412, 95% CI 0.190–0.892, P = 0.024 and OR 0.367, 95% CI 0.161–0.840, P = 0.018) were significant variables for the live birth rate in POSEIDON Group 2.ConclusionsThe findings in the present study showed that eSET was preferred in the first frozen cycle for POSEIDON Group 1 to avoid unnecessary risks. Double embryo transfer strategy could be considered to improve the success rate for POSEIDON Group 2 with caution. Further stratification by age is needed for a more scientific discussion about the embryo transfer strategy for POSEIDON patients.

In vitro Fertilization Outcomes of Frozen-thawed Embryo Transfer with Hatched Blastocysts versus with Hatching Blastocysts.

This study aimed to elucidate the effect of hatching status on in vitro fertilization (IVF) outcomes in frozen-thawed blastocyst transfer cycles. Frozen-thawed embryo transfer (FET) cycles performed at a single fertility center between 2016 and 2021 were retrospectively assessed. Analyses were restricted to 6,821 frozen-thawed blastocyst transfers in women aged 24-47 years. For optimal comparability, double embryo transfer (ET) cycles consisting of one hatching and one hatched blastocyst were excluded. The implantation and pregnancy rates were evaluated and compared between the hatching and hatched blastocyst transfer groups based on patients' age (<38 vs. ≥38 years), blastocyst grade (good vs. bad grade), and the number of transferred embryos (single ET vs. double ET). Hatched blastocyst transfer was associated with higher implantation and clinical pregnancy rates in the single ET group (15.7% and 15.6%, respectively; p<0.001). The transfer of two hatched blastocysts had higher implantation and clinical pregnancy rates compared to the transfer of two hatching blastocysts (19.5% and 20.4%, respectively; p<0.001) in the double ET group. In the hatched blastocyst transfer group, the clinical pregnancy and implantation rates were higher, regardless of each woman's age and embryo quality. The IVF treatment outcomes were improved when the blastocysts were hatched during FET cycles. Hence, hatched blastocyst transfer in FET cycles could be considered a superior method in IVF practice.

Safety profiles of offspring born from early-follicular long-acting GnRH agonist protocol and daily mid-luteal GnRH agonist protocol: a retrospective study

BackgroundThe gonadotropin hormone-releasing hormone agonists (GnRH-a) have been widely used for controlled ovarian stimulation in assisted reproductive technology (ART). The early-follicular long-acting GnRH-a long protocol (EFL) and the luteal phase short-acting GnRH-a long protocol (LPS) are commonly used GnRH agonist protocols. We conducted a retrospective analysis to assess and compare the rates of congenital abnormalities and safety profiles in offspring born from the EFL and LPS protocols.MethodsWe conducted a retrospective cohort study to analyze and compare neonatal data from patients who using EFL or LPS protocols at our center between January 1, 2014, and June 30, 2017. The study ultimately included 1810 neonates from 1401 cycles using the EFL protocol and 2700 neonates from 2129 cycles using the LPS protocol.The main outcome measures are gestational age at delivery, birth weight, and congenital anomaly rate.To assess the influence of various factors on congenital abnormalities, a random-effects logistic regression model was employed.ResultsThe EFL and LPS protocols led to similar congenital anomaly rates (1.64% vs. 2.35%, P = 0.149). No significant differences were found between the two groups regarding birth weight and its categories, newborn gender and congenital anomaly rate. The results of the multivariate logistic regression model indicated no association between congenital anomaly and BMI, duration of infertility, treatment protocol, fertilization method, or embryo transfer stage. Compared with singleton pregnancies, the probability of congenital defects in multiple pregnancies was 2.64 times higher (OR: 2.64, 95% CI: 1.72–4.05, P < 0.0001). Newborns with congenital defects were born with a lower gestational age compared with full-term pregnancies.ConclusionIn conclusion, the EFL protocol is considered a safe option for ensuring offspring safety, comparable with the LPS protocol; however, multiple pregnancies represent an independent risk factor for congenital abnormalities. This approach can be widely adopted; however, prioritizing single embryo transfers is strongly recommended to minimize the potential risks associated with multiple pregnancies in offspring.

IVF and obstetric outcomes among women of advanced maternal age (≥45 years) using donor eggs

Research questionDoes very advanced maternal age (VAMA; age ≥45 years) influence obstetric outcomes among women using donor oocytes in IVF? DesignThis retrospective cohort study analysed data from a nationwide IVF registry in Taiwan, focusing on IVF cycles involving women aged 45 years and older using donated oocytes between 2007 and 2016. The study assessed cumulative live birth rates (CLBR) and secondary outcomes such as clinical pregnancy, miscarriage, live birth and twin pregnancy rates, alongside perinatal outcomes such as Caesarean section rates, pre-eclampsia, gestational diabetes and birthweight. ResultsThe study included 1226 embryo transfer cycles from 745 women, with a stable live birth rate of about 40% across the study period. The CLBR was slightly lower in women aged 50 years and older (54.2%) compared with those aged 45–46 years (58.0%), but these differences were not statistically significant (P = 0.647). Secondary outcomes and perinatal outcomes did not significantly differ across age groups. Regression analysis suggested a non-significant trend towards a decrease in live birth rate and birthweight with increasing maternal age. The study also found that single-embryo transfer (SET) minimized the risk of twin pregnancies without significantly affecting live birth rates. ConclusionsIVF with donor oocytes remains a viable option for women of VAMA, with consistent live birth rates across age groups. However, the study underscores the importance of elective SET to reduce the risk of twin pregnancies and associated adverse outcomes. Further research is needed to explore the impact of other factors such as paternal age and embryo development stage on IVF success in this population.

Is biochemical pregnancy loss associated with embryo or endometrium? A retrospective cohort study in frozen single embryo transfer of own and donated oocytes.

Does the use of preimplantation genetic testing for aneuploidies (PGT-A), personalized embryo transfer with endometrial receptivity assay (pET-ERA), or the use of donated oocytes modify the incidence of biochemical pregnancy loss (BPL) in frozen single embryo transfer (FSET)? Following FSET, BPL incidence does not differ between own and donated oocytes, and the use of PGT-A with euploid embryo transfer or pET-ERA results in a similar incidence of BPL compared to cycles without embryo or endometrial analysis. BPL occurs frequently after IVF, and many factors have been associated with its incidence. The etiology of BPL is not well known, but the most probable cause seems to be either a low-quality embryo or impaired endometrial maintenance. The impact of techniques diagnosing embryonic ploidy or endometrial receptivity on BPL incidence and the BPL incidence between own and donated oocytes have not been analyzed. This is a retrospective cohort study analyzing the incidence of BPL over 3741 cycles of FSET derived from own (2399 cycles) and donated (1342 cycles) oocytes between January 2013 and January 2022 in 1736 of which PGT-A, pET-ERA, or both were applied. We defined BPL as a pregnancy diagnosed only by serum β-hCG > 10 UI/l followed by a decrease that does not result in a clinical pregnancy. Clinical pregnancy was defined as the presence of gestational sac on transvaginal ultrasound. We compared BPL rates among patients undergoing 2399 FSETs from own oocytes, which comprised 1310 cycles of embryos analyzed by PGT-A, 950 cycles of untested embryos, 30 cycles of untested embryos with pET-ERA, and a subgroup of 109 cycles analyzed by both PGT-A and pET-ERA. We also included a total of 1342 FSET cycles from donated oocytes comprising 132, 1055, 140, and 15 cycles in the same groups, respectively. In FSET from own oocytes, the overall BPL rate per embryo transfer was 8.2% (95% CI [7.09-9.33]). In untested embryo transfers, the BPL rate was 7.5% [5.91-9.37]. In the PGT-A group, the BPL rate was 8.8% [7.32-10.47]. In the pET-ERA group, the rate was 6.7% [0.82-22.07]. In the PGT-A+ERA group, the rate was 6.5% [2.65-12.90]. No significant differences were found (P = 0.626). A multivariate analysis considering clinically meaningful variables that were significantly different among groups, taking the untested embryos/endometrium group as a reference, showed comparable incidences among groups. For PGT-A, the adjusted odds ratio (AdjOR) was 1.154 [0.768-1.735] (P = 0.49) and for PGT-A+ERA 0.885 [0.330-2.375] (P = 0.808). Because of a low number of registered cases in the pET-ERA group, and to prevent statistical errors and convergence issues, this group was excluded from further analysis. In FSET of donated oocytes, the overall BPL rate per embryo transfer was 4.9% [3.76-6.14]. In the PGT-A group, the BPL rate was 6.8% [3.16-12.55]. In the pET-ERA group, the rate was 5.0% [2.03-10.03]. In untested embryo transfers, the rate was 4.7% [3.46-6.10]. No cases occurred in the PGT-A+ERA group, and no significant differences were found (P = 0.578). The multivariate analysis showed comparable incidences among groups. For PGT-A the AdjOR was 1.669 [0.702-3.972] (P = 0.247) and for pET-ERA 1.189 [0.433-3.265] (P = 0.737). The PGT-A+ERA group was eliminated from the model to prevent statistical errors and convergence issues because no BPL cases were registered in this group. In the multivariate analysis, when the sources of oocytes were compared, own versus donated, no significant differences were found in the incidence of BPL. This was a retrospective cohort study with potential biases. In addition, we were unable to control differences among groups due to modifications in medical or laboratory protocols during this long time period, which may modify the relationships being addressed. Factors previously associated with BPL, such as immunological conditions other than thyroid autoimmunity, were not considered in this study. Limited sample sizes of some groups may limit the statistical power for finding differences that can be present in the general population. BPL may be related to a mechanism not associated with the chromosomal constitution of the embryo or the transcriptome of the endometrium. More studies are needed to explore the factors associated with this reproductive issue. No specific funding was available for this study. None of the authors have a conflict of interest to declare with regard to this study. This trial was registered at clinicaltrials.gov (NCT04549909).

Gestational carrier cycles: embryology trends, national guideline compliance, and resultant perinatal outcomes in the United States, 2014–2020

The increased use of gestational carriers has expanded family-building opportunities for people and couples unable to carry pregnancies on their own. National American Society of Reproductive Medicine guidelines for gestational carriers have changed over time to reflect advances in reproductive technology and mounting evidence supporting the medical benefits associated with singleton gestations. Assess changes in gestational carrier cycle practice patterns and resultant pregnancy outcomes in the United States in relation to changing national American Society of Reproductive Medicine guidelines, which changed in 2013 and2017. This retrospective study used data from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System and included all cycles that were reported from 2014-2020 involving an embryo transfer to a gestational carrier. Binomial regression models evaluated trends in preimplantation genetic testing for aneuploidy, American Society of Reproductive Medicine guideline adherence, number of embryos transferred, and pregnancy outcomes over time. Of the 40,177 gestational carrier transfer cycles from 2014-2020, there was a significant increase in frozen-thawed cycles (41.3% increase), use of assisted hatching (53.4% increase), intracytoplasmic sperm injection (50.0% increase), and preimplantation genetic testing for aneuploidy (155.7% increase). The likelihood of preimplantation genetic testing for aneuploidy was higher in 2020 than in 2014 for autologous oocyte transfers to gestational carriers, both for those aged ≥38 years (adjusted relative risk, 2.38 [95% confidence interval, 2.11-2.70]) and than those aged <38 years (adjusted relative risk, 2.85 [95% confidence interval, 2.58-3.15]). As preimplantation genetic testing for aneuploidy usage increased, single embryo transfer rose for both autologous (adjusted relative risk, 2.22 [95% confidence interval, 1.94-2.50]) and donor cycles (relative risk, 1.91 [95% confidence interval, 1.81-2.02]). This shift toward single embryo transfer corresponded with a decrease in multiple embryo transfer by 79.2% and subsequent decreases in multiple gestations by 68.8% in donor and 73.6% in autologous oocyte cycles from 2014-2020. Gestational carrier cycles remained highly adherent to changing American Society of Reproductive Medicine guidelines throughout the study period. Among live births, there was a 19.4% and 7.9% increase in term deliveries among donor and autologous oocyte cycles, respectively, from 2014 to2020. Practice patterns have drastically changed throughout the study period, with major increases in the use of preimplantation genetic testing for aneuploidy, intracytoplasmic sperm injection, assisted hatching, and frozen transfers. In response to changing American Society of Reproductive Medicine guidelines, the use of multiple embryo transfers has decreased for gestational carrier cycles with subsequent decreases in multiple gestations and miscarriages and slight increases in live birth rates.

Twins Standing in for Co-Twins: Explanation and Speculation/Twin Research Reviews: Single v. Multiple Embryo Transfer; Neurimaging of Twins with Periventricular Nodular Heterotopia; Twin Dietary Study; New Hungarian Text on Twins/Human Interest: Valedictorian and Salutatorian Twins; Twin Mother at Age Seventy; Twins Reunited by Tiktok; New Film on Twins with Selective Mutism; Becoming Twin Doctors.

An overview of circumstances in which twins take the place of their co-twin is presented. Various explanations and speculations are proposed for understanding twins' willingness to do so in certain situations. This section is followed by reviews of timely twin research, namely single versus multiple embryo transfer; neurimaging of twins with periventricular nodular heterotopia; a twin dietary comparison; and a new book of twin-related readings from Hungary. The final portion of this article concerns human interest stories that both inform and entertain. They involve valedictorian and salutatorian twins; a mother delivering twins at age seventy; twins reunited by TikTok; a new film about twins with selective mutism; and twins becoming doctors.

Association between the length of in vitro embryo culture, mode of ART, and the initial endogenous hCG rise in ongoing singleton pregnancies.

Is there an association between the length of in vitro culture, mode of ART and the initial endogenous hCG rise, in cycles with a foetal heartbeat after single embryo transfer (ET) and implantation? Both the length of in vitro culture and the mode of ART have an impact on the initial endogenous rise in hCG in singleton pregnancies. Different factors have been identified to alter the kinetics of hCG in pregnancies. Current studies show conflicting results regarding the kinetics of hCG after different types of ART (fresh vs frozen ET (FET)), the inclusion or not of preimplantation genetic testing (PGT), and the length of time in in vitro culture. This was a multicentre cohort study, using prospectively collected data derived from 4938 women (5524 treatment cycles) undergoing IUI (cycles, n = 608) or ART (cycles, n = 4916) treatments, resulting a in singleton ongoing pregnancy verified by first-trimester ultrasound scan. Data were collected from the Danish Medical Data Centre, used by the three participating Danish public fertility clinics at Copenhagen University hospitals: Herlev Hospital, Hvidovre Hospital, and Rigshospitalet, from January 2014 to December 2021. The fresh ET cycles included cleavage-stage (2 or 3 days in vitro) and blastocyst (5 days in vitro) transfers. FET cycles included cleavage-stage (3 days in vitro before cryopreservation) or blastocyst (5 or 6 days in vitro before cryopreservation) transfers. The IUI cycles represented no time in vitro. To attain a comparable interval for serum-hCG (s-hCG), the ovulation induction time was identical: 35-37 h before oocyte retrieval or IUI. The conception day was considered as: the insemination day for pregnancies conceived after IUI, the oocyte retrieval day for fresh ET, or the transfer day minus 3 or 5 as appropriate for FET of Day 3 or 5 embryos. Multiple linear regression analysis was used, including days post-conception for the hCG measurement as a covariate, and was adjusted for the women's age, the cause of infertility, and the centre. For FET, a sensitivity analysis was used to adjust for endometrial preparation. The study totally includes 5524 cycles: 2395 FET cycles, 2521 fresh ET cycles, and 608 IUI cycles. Regarding the length of in vitro culture, with IUI as reference (for no time in in vitro culture), we found a significantly lower s-hCG in pregnancies achieved after fresh ET (cleavage-stage ET or blastocyst transfer). S-hCG was 18% (95% CI: 13-23%, P < 0.001) lower after fresh cleavage-stage ET, and 23% (95% CI: 18-28%, P < 0.001) lower after fresh blastocyst transfer compared to IUI. In FET cycles, s-hCG was significantly higher after blastocyst transfers compared to cleavage-stage FET, respectively, 26% (95% CI: 13-40%, P < 0.001) higher when cryopreserved on in vitro Day 5, and 14% (95% CI: 2-26%, P = 0.02) higher when cryopreserved on in vitro Day 6 as compared to Day 3. Regarding the ART treatment type, s-hCG after FET blastocyst transfer (Day 5 blastocysts) cycles was significantly higher, 33% (95% CI: 27-45%, P < 0.001), compared to fresh ET (Day 5 blastocyst), while there was no difference between cleavage-stage FET (Days 2 + 3) and fresh ET (Days 2 + 3). S-hCG was 12% (95% CI: 4-19%, 0.005) lower in PGT FET (Day 5 blastocysts) cycles as compared to FET cycles without PGT (Day 5 blastocysts). The retrospective design is a limitation which introduces the risk of possible bias and confounders such as embryo score, parity, and ovarian stimulation. This study elucidates how practices in medically assisted reproduction treatment are associated with the hCG kinetics, underlining a potential impact of in vitro culture length and mode of ART on the very early embryo development and implantation. The study provides clinicians knowledge that the type of ART used may be relevant to take into account when evaluating s-hCG for the prognosis of the pregnancy. No funding was received for this study. AP has received consulting fees, research grants, or honoraria from the following companies: Preglem, Novo Nordisk, Ferring Pharmaceuticals, Gedeon Richter, Cryos, Merck A/S, and Organon. AZ has received grants and honoraria from Gedeon Richter. NLF has received grants from Gedeon Richter, Merck A/S, and Cryos. MLG has received honoraria fees or research grants from Gedeon Richter, Merck A/S, and Cooper Surgical. CB has received honoraria from Merck A/S. MB has received research grants and honoraria from IBSA. MPR, KM, and PVS all report no conflicts of interest. The study was registered and approved by the Danish Protection Agency, Capital Region, Denmark (Journal-nr.: 21019857). No approval was required from the regional ethics committee according to Danish law.

Effect of intraovarian platelet-rich plasma injection on IVF outcomes in women with poor ovarian response: the PROVA randomized controlled trial.

Does intraovarian platelet-rich plasma (PRP) injection increase the number of mature oocytes obtained after controlled ovarian stimulation (COS) in young women with poor ovarian response (POR) undergoing IVF? Intraovarian PRP injection procedure does not improve mature oocyte yield after COS in women less than 38 years old with an established IVF history of POR. POR is frequently encountered among the infertile population and the number of women seeking infertility treatment related to POR is increasing. Effective treatment options for this patient population to conceive with autologous oocytes are lacking. Case series and cohort studies suggest that intraovarian PRP injection may improve follicular recruitment in women with premature ovarian insufficiency (POI) and POR, yet robust randomized studies have not been performed to date to determine the clinical utility of this intervention. This was a multi-center randomized controlled trial (RCT) conducted at university-affiliated reproductive centers in the USA and Turkey, between January 2020 and November 2022. Patients who met inclusion criteria (<38 years old, two or more prior cycles with <3 oocytes retrieved; and without single gene disorders, prior ovarian surgery, endometriomas, BMI >35 kg/m2, or severe male factor infertility) were randomized to either the PRP or control group. Patients in both groups subsequently underwent COS, oocyte retrieval, ICSI, preimplantation genetic testing for aneuploidy (PGT-A), and single euploid embryo transfer. Number of metaphase II (MII) oocytes obtained was the primary outcome. Secondary outcomes included ovarian reserve tests (antral follicle count [AFC] and anti-Müllerian hormone [AMH]), blastocyst and euploid blastocyst yields, and sustained implantation. The study was powered to detect a difference of one mature oocyte obtained at oocyte retrieval. In total, 83 patients met inclusion criteria and were randomized to receive autologous intraovarian PRP injection (n = 41) or to no intervention (n = 42). No significant differences were observed in number of MII oocytes retrieved per cycle (2.8 ± 2.4 vs 3.1 ± 3.3 in PRP vs control, respectively; P = 0.9), blastocysts (1.0 ± 1.3 vs 1.3 ± 2.1, P = 0.8), or euploid blastocysts (0.8 ± 1.1 vs 0.9 ± 1.6; P = 0.5). Similarly, no differences were observed in the likelihood of obtaining at least one euploid blastocyst (45% vs 37%, P = 0.4; relative risk [RR], 95% CI = 0.9, 0.6-1.2) or the rate of sustained implantation (31% vs 29%, P = 0.9; RR 1.0, 0.7-1.3). Posttreatment AFC (7.9 ± 4.5 vs 6.8 ± 4.8, P = 0.3) and AMH (0.99 ± 0.98 vs 0.7 ± 0.6, P = 0.2) were also not different between the groups. Results from this RCT may not be generalizable to other PRP preparations owing to heterogeneity and lack of standardization. The control groups did not undergo a sham ovarian injection, which would have been relevant had the results shown benefit of PRP injection. Only patients with POR were included in this study, and these results may not be generalizable to more severe diminution of ovarian reserve, as seen with POI. The intraovarian PRP injection procedure does not improve mature oocyte yield or other parameters of IVF outcome in women less than 38 years old with an established IVF history of POR. The results from this study do not support the use of intraovarian PRP injection in this population. Departmental funds were used and no external funding was requested for this study. ES is a consultant for and receives grant funding from the Foundation for Embryonic Competence. All other authors have no conflict of interest to declare. Clinicaltrials.gov Registry Identifier: NCT04163640. 15 November 2019. 24 February 2020.