OBJECTIVE: 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?
CONCLUSIONS: 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.
BACKGROUND: 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.
METHODS: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
CONCLUSIONS: 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.
BACKGROUND: 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.
BACKGROUND: The RCT was registered in the Chinese Clinical Trial Registry; Study Number: ChiCTR2100053453.
UNASSIGNED: 21 November 2021.
UNASSIGNED: 23 November 2021.

BACKGROUND: In addition to the potential for multiple pregnancies, natural conception occurring in preimplantation genetic testing (PGT) increases undesired genetic risk. Some studies showed that a dichorionic diamniotic twin pregnancy after a single blastocyst transfer could be caused by embryo splitting or concurrent spontaneous conception.
METHODS: We describe a patient undergoing PGT who had a dichorionic diamniotic twin pregnancy after single blastocyst transfer in a natural cycle. In this case, we recommended to determine genetic status of the twins by prenatal diagnosis. The results showed that karyotype, chromosome copy number variation, and parental ACAT1 variation of the twins were all normal and similar. To investigate the origin of pregnancy, we used the genotype data of single-nucleotide polymorphisms typical of genome-wide association studies. Dizygotic twins were inferred by robust estimation of kinship coefficients, which confirmed the occurrence of a spontaneous conception.
CONCLUSIONS: This case strengthens the importance of genetic counseling to inform couples with reproductive genetic risk, such as those who undergo PGT, that intercourse should be avoided, especially in natural transfer cycles. Moreover, prenatal diagnosis remains essential and is strongly recommended to avoid genetic risks.

Among the primary objectives of contemporary assisted reproductive technology research are achieving the births of healthy singletons and improving overall fertility outcomes. Substantial advances have been made in refining the selection of single embryos for transfer, with the aim of maximizing the likelihood of successful implantation. The principal criterion for this selection is embryo morphology. Morphological evaluation systems are based on traditional parameters, including cell count and fragmentation, pronuclear morphology, cleavage rate, blastocyst formation, and various sequential embryonic assessments. To reduce the incidence of multiple pregnancies and to identify the single embryo with the highest potential for growth, invasive techniques such as preimplantation genetic screening are employed in in vitro fertilization clinics. However, new approaches have been suggested for clinical application that do not harm the embryo and that provide consistent, accurate results. Noninvasive technologies, such as time-lapse imaging and omics, leverage morphokinetic parameters and the byproducts of embryo metabolism, respectively, to identify noninvasive prognostic markers for competent single embryo selection. While these technologies have garnered considerable interest in the research community, they are not incorporated into routine clinical practice and still have substantial room for improvement. Currently, the most promising strategies involve integrating multiple methodologies, which together are anticipated to increase the likelihood of successful pregnancy.

OBJECTIVE: To evaluate in vitro fertilization (IVF) and perinatal outcomes of donor egg and autologous cycles in advanced reproductive-aged patients after undergoing single, frozen euploid embryo transfer (SET/FET).
METHODS: A retrospective, multicenter cohort study.
METHODS: University-affiliated and private IVF centers.
METHODS: Patients between 39-46 years old undergoing IVF with intracytoplasmic sperm injection (ICSI) and preimplantation genetic testing for aneuploidy (PGT-A) using whole-chromosome sequencing with donor (n=278) or autologous (n=278) oocytes between October 2017 and October 2021.
METHODS: SET/FET with donor or autologous euploid embryo MAIN OUTCOME MEASURE(S): The live birth rate after the first embryo transfer, calculated per embryo transfer. Secondary outcomes included implantation rate, ectopic pregnancy rate, miscarriage rate, and gestational age and birthweight at the time of delivery.
RESULTS: Patients using donor or autologous oocytes had a similar likelihood of implantation 57.91% (51.87-63.78) versus 57.19% (51.15-63.09), p=0.93 and live birth rate 41.01% (95% CI:35.17-47.04) versus 42.45% (95% CI:36.56-48.49), p=0.86. Furthermore, there were no significant differences in ectopic pregnancy rate [0.72% (0.09-2.57) versus 0.36% (0.01-1.99), p=1] or miscarriage rate [16.19% (12.06-21.05) versus 14.39% (95% CI:10.48-19.08), p=0.98], gestational age [38.50 weeks (38.08-38.92) versus 39.16 weeks (38.25-40.07), p=0.19], or birthweight of infants [2982.25 kg (2606.69-3357.81) versus 3128.24 kg (2962.30-3294.17), p=0.95]. The univariate analysis showed no association of advanced maternal age on the live birth rate [risk relative (RR) 1.03 (IC95%: 0.84-1.25); p=0.79]. Multivariate analysis using putative confounders for embryo competency found no associations with live birth rate [adjusted risk relative (aRR) 1.22 (IC95%: 0.75-1.98); p=0.42] CONCLUSION(S): Patients with euploid blastocysts derived from donor or autologous oocytes did not reveal statistically significant differences in live birth rate, implantation rate, ectopic pregnancy rate, miscarriage rate, duration of gestation, or infant birthweight. These findings suggest that age-related reproductive decline and/or poor IVF outcomes associated with advanced reproductive-aged women undergoing IVF are heavily driven by embryonic aneuploidy.

Essential trace elements are micronutrients whose deficiency has been associated with altered fertility and/or adverse pregnancy outcomes, while surplus may be toxic. The concentrations of eight essential trace elements were measured using inductively coupled mass spectrometry (ICP-MS) and assessed with respect to clinical in vitro fertilization (IVF) outcomes in a population of 51 women undergoing IVF with intracytoplasmic sperm injection (ICSI), pre-implantation genetic screening for aneuploidy (PGT-A), and single frozen euploid embryo transfer (SET/FET). Specifically, copper (Cu), zinc (Zn), molybdenum, selenium, lithium, iron, chromium, and manganese were quantified in follicular fluid and whole blood collected the day of vaginal oocyte retrieval (VOR) and in urine collected the day of VOR and embryo transfer. We found that the whole blood Cu/Zn ratio was significantly associated with superior responses to ovarian stimulation. Conversely, the whole blood zinc and selenium concentrations were significantly associated with poor ovarian response outcomes. Higher levels of whole blood zinc and selenium, urinary selenium, lithium, and iron had significant negative associations with embryologic outcomes following IVF. Regarding clinical IVF outcomes, higher urinary molybdenum concentrations the day of VOR were associated with significantly lower odds of implantation and live birth, while higher urinary Cu/Mo ratios on the day of VOR were associated with significantly higher odds of implantation, clinical pregnancy, and live birth. Our results suggest that essential trace element levels may directly influence the IVF outcomes of Spanish patients, with selenium and molybdenum exerting negative effects and copper-related ratios exerting positive effects. Additional studies are warranted to confirm these relationships in other human populations.

BACKGROUND: Prospective observational studies have demonstrated that the machine learning (ML) -guided noninvasive chromosome screening (NICS) grading system, which we called the noninvasive chromosome screening-artificial intelligence (NICS-AI) grading system, can be used embryo selection. The current prospective interventional clinical study was conducted to investigate whether this NICS-AI grading system can be used as a powerful tool for embryo selection.
METHODS: Patients who visited our centre between October 2018 and December 2021 were recruited. Grade A and B embryos with a high probability of euploidy were transferred in the NICS group. The patients in the control group selected the embryos according to the traditional morphological grading. Finally, 90 patients in the NICS group and 161 patients in the control group were compared statistically for their clinical outcomes.
RESULTS: In the NICS group, the clinical pregnancy rate (70.0% vs. 54.0%, p < 0.001), the ongoing pregnancy rate (58.9% vs. 44.7%, p = 0.001), and the live birth rate (56.7% vs. 42.9%, p = 0.001) were significantly higher than those of the control group. When the female was ≥ 35 years old, the clinical pregnancy rate (67.7% vs. 32.1%, p < 0.001), ongoing pregnancy rate (56.5% vs. 25.0%, p = 0.001), and live birth rate (54.8% vs. 25.0%, p = 0.001) in the NICS group were significantly higher than those of the control group. Regardless of whether the patients had a previous record of early spontaneous abortion or not, the live birth rate of the NICS group was higher than that of the control group (61.0% vs. 46.9%; 57.9% vs. 34.8%; 33.3% vs. 0%) but the differences were not statistically significant.
CONCLUSIONS: NICS-AI was able to improve embryo utilisation rate, and the live birth rate, especially for those ≥ 35 years old, with transfer of Grade A embryos being preferred, followed by Grade B embryos. NICS-AI can be used as an effective tool for embryo selection in the future.

BACKGROUND: 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.
OBJECTIVE: 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 and 2017.
METHODS: 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.
RESULTS: 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 to 2020.
CONCLUSIONS: 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.

BACKGROUND: In recent years, the use of frozen embryo transfers (FET) has rapidly increased following the freeze-all strategy due to the advantages of increased maternal safety, improved pregnancy rates, lower ectopic pregnancy rates and better obstetric and neonatal outcomes. Currently, there is still no good scientific evidence to support when to perform FET following a stimulated in vitro fertilisation (IVF) cycle in the freeze-all strategy.
METHODS: This will be a randomised controlled trial. A total of 828 women undergoing their first FET following their first stimulated IVF cycle in the freeze-all strategy will be enrolled and randomised into one of the following groups according to a computer-generated randomisation list: (1) the immediate group, in which FET will be performed in the first menstrual cycle following the stimulated IVF cycle; or (2) the delayed group, in which FET will be performed at least in the second menstrual cycle following the stimulated IVF cycle. The primary outcome will be live birth, which is defined as the delivery of any infants at ≥22 gestational weeks with heartbeat and breath.
UNASSIGNED: Ethical approval was granted by the Ethics Committee of Assisted Reproductive Medicine at the Shanghai JiAi Genetics & IVF Institute (JIAI E2019-15). Written informed consent will be obtained from each woman before any study procedure is performed, according to good clinical practice. The results of this trial will be disseminated in a peer-reviewed journal.
BACKGROUND: NCT04371783.

OBJECTIVE: This study aimed to compare the per OPU clinical outcomes for transfer of Day 3 double cleavage-stage embryos (DET) and Day 5 single blastocyst-stage (SBT) in patients with five or fewer good quality embryos on day 3 per occyte pick-up cycle (OPU) in antagonist cycles with consideration of blastocyst formation failure.
METHODS: This was a retrospective, observational cohort study of 2,116 cases of OPU treated with antagonist protocol in the affiliated Chenggong Hospital of Xiamen University between January 2013 and December 2020. DET was performed in 1,811cycles and SBT was performed in 305 cycles. The DET group was matched to the SBT group by propensity score (PS) matching according to multiple maternal baseline covariates. After PS matching, there were 303 ET cycles in each group. The primary outcomes were the cumulative live birth rate (CLBR), cumulative multiple pregnancy rate(CMPR)per OPU and the number of ET to achieve live birth per OPU. Secondary outcomes were the percentage of clinical pregnancy(CPR), live birth rate(LBR), multiple pregnancy rate(MPR).
RESULTS: Following PS mating, the CLBR was slightly higher (48.8% versus 40.3% ; P = 0.041) and the CMPR was significantly higher in the DET group compared to SBT group(44.2% versus 7.9%, P < 0.001). The CPR, LBR and MPR per fresh transfer were higher in DET group compared to SBT group(50.2% versus 28.7%; 41.3% versus 21.5%;29.6% versus 0%, P < 0.001). The number of ET to achieve live birth per OPU in SBT group was obiviously more than in DET group(1.48 ± 0.578 versus 1.22 ± 0.557 ,P < 0.001).
CONCLUSIONS: With a marginal difference cumulative live birth rate, the lower live birth rate per fresh transfer and higher number of ET per OPU in the SBT group suggested that it might take longer time to achieve a live birth with single blastocyst strategy. A trade-off decision should be made between efficiency and safety.

The sex ratio shift was observed in peoples who underwent ART treatment. Moreover, there is limited evidence on differences in sex ratio between single frozen-thawed blastocyst morphology, insemination type and transfer days. So further research is needed in this area with regard to factors possibly affecting the sex ratio. Retrospective study based on multicenter including two large assisted reproduction centers in Shanghai and Wuhan in China. A total of 6361 singleton delivery offspring after frozen-thawed blastocyst transfer. Propensity score weighting and logistic regression models were used to estimate the associations between blastocyst morphology grading and child sex ratio. The main outcome measures is singleton sex ratio. In our study, the primary outcome measure was sex ratio which was calculated as the proportion of male newborns among all live births. Higher quality blastocysts resulted in a higher sex ratio than single poor-quality frozen-thawed blastocyst transfer. Among the three blastocyst morphological parameters of trophectoderm (TE), Grade A and B were significantly associated with a higher sex ratio than Grade C. The similar trend was observed in both IVF and ICSI treated subgroups. As compared with expansion (4 + 3), expansion degree 6 achieved a higher sex ratio in overall populations and IVF treated subgroup. Transferring blastocysts of day 6 had the highest sex ratio both in IVF group and ICSI group. A 6.95% higher sex ratio in transferring blastocysts of day 5 in IVF group than those in ICSI group. No significant association between inner cell mass degree and sex ratio was observed. However, as compared with IVF treatment, all morphology parameters achieved the similar or the biased sex ratio favoring female in ICSI treated subgroup. Quality of blastocysts was positively associated with sex ratio. TE score and expansion degree rather than ICM were significantly associated with sex ratio at birth. ICSI treatment promotes the biased sex ratio favoring female.