Cleavage-stage Embryo Transfer Research Articles

Blastocyst versus cleavage transfers: who benefits?

This retrospective cohort study determined the relative efficacy of blastocyst and cleavage-stage transfers in patients with differing numbers of zygotes. A total of 1116 women whose embryo transfers were planned independently of patient characteristics were included. Cleavage-stage (D3) and blastocyst-stage (D5) transfer outcomes were analyzed per number of zygotes. The D5 group included transfer cancellations as the intention-to-treat population. The effect of the embryo transfer date on the clinical outcomes (clinical pregnancy and implantation rates) was analyzed using multivariate logistic regression. Among the patients, 584 and 532 underwent D3 and D5 embryo transfers, respectively. The clinical pregnancy rates were significantly higher in D5 patients with ≥ 6 zygotes (25.7% vs 48.3%). The multivariate logistic regression analysis for clinical pregnancy did not show significant differences between the blastocyst and cleavage-stage transfers in patients with ≤ 5 zygotes (0.874[0.635-1.204]). Compared to the cleavage-stage, blastocyst-stage transfers for patients with ≥ 6 zygotes resulted in a three-fold increase in clinical pregnancy rates (3.122[1.797-5.425]). Blastocyst transfers were not inferior to cleavage-stage embryo transfers among patients with few zygotes and were preferable for patients with several zygotes.

THE EFFICACY OF PHYSIOLOGICAL SPERM SORTING IN ADDITION TO MORPHOLOGICAL SORTING

Selection of spermatozoa is one of the most important factors that influence embryonic development and clinical outcome in intracytoplasmic sperm injection (ICSI). Intracytoplasmic morphologically selected sperm injection (IMSI) is a technique that selects spermatozoa only according to their morphologically features under high magnification. However, there is another sperm selection technique that uses hyaluronic acid (HA) to select physiologically mature spermatozoa (HA-ICSI). The purpose of this study is to investigate the efficacy of physiological sperm sorting in addition to morphological sorting, and how this could contributes to subsequent embryonic development and clinical outcomes. Study 1: A total of 658 mature (MII) oocytes derived from large follicles obtained under letrozole cycle were enrolled between April 2017 and May 2020. Sperm sorting using HA was performed with SpermSlow™ (ORIGIO). The normal fertilization rates, abnormal fertilization rates, egg degeneration rates, cleavage rates, blastocyst formation rates, blastocyst freezing rates, and good quality blastocyst rates at freezing were compared between the two groups (339 oocytes in the IMSI group (April 2017 to April 2018) and 319 oocytes in the HA-IMSI group (April 2018 to May 2020)). Study 2: Clinical pregnancy rates (CPR), live birth rates (LBR), and abortion rates of day 2 fresh cleavage stage embryo transfer (d2ET) were compared between the IMSI group and the HA-IMSI group. A total of 128 patients (age 34–40 years) out of 225 patients (age 37.1± 4.1 years ) who underwent d2ET of their first treatment cycle between January 2017 and December 2019 were enrolled. Written informed consent was obtained from all participants. Study 1: The blastocyst freezing rates of participants that were <40 years of age was significantly higher in the HA-IMSI group (73.3% vs. 58.0%, p<0.05) than in the IMSI group. The rates of egg degeneration of participants that were >40 years of age was significantly lower in the HA-IMSI group (0.7% vs. 5.2%, p<0.05) that in the IMSI group. Other parameters also showed favorable trends in the HA-IMSI group, but were not statistically significant. Study 2: The CPR and LBR were significantly higher in the HA-IMSI group (18.2% vs 34.2%, p<0.05 14.6% vs 32.9%, p<0.05 respectively) than in the IMSI group. There was no significant differences in abortion rates. Blastocyst freezing rates in participants that were <40 years of age was significantly higher in the HA-IMSI group than in the IMSI group, and this suggests that the effect of physiological sperm sorting using HA is more remarkable when the quality of the oocyte is guaranteed.

Oocyte Degeneration After ICSI Is Not an Indicator of Live Birth in Young Women.

IntroductionIntracytoplasmic sperm injection (ICSI) was introduced in 1990s as one of the most dramatic breakthroughs in assisted reproductive technology. Even with advances in ICSI technology, this mechanical micromanipulation carries a 5 to 19% risk of oocyte degeneration. Whether the presence of oocyte degeneration reflects the sibling oocyte quality and predicts the sibling embryo development potential and clinical pregnancy outcomes remains controversial. There is no study showing the competence of the sibling embryos from the prospective of cumulative live birth rate. Whether oocyte degeneration is associated with poor quality of the remainder of the cohort remains further to be elucidated.MethodThis retrospective observational study included a total of 488 OPU cycles underwent ICSI with fresh cleavage stage embryo transfer and successive frozen/thawed embryo transfer (FET) cycles from January 2018 to December 2019. All female patients were under the age of 35 years, and underwent ICSI with or without oocyte degeneration (OD). Cycles with at least one oocyte degenerated were defined as oocyte degeneration group (OD group), and cycles with no oocyte degenerated were defined as non-OD group. The OD group was further divided to three subgroups according to different oocyte degeneration rate (<10%, 10-20%, and >20%).ResultsThere were no significant differences with regards to implantation rate (38.5% vs 35.1%, P=0.302), clinical pregnancy rate (54.9% vs 50.3%, P=0.340), and LBR per OPU cycle (47.0% vs 42.9%, P=0.395) between OD and non-OD groups. Initial gonadotropin dosage, E2 level on hCG day and the number of matured oocytes appeared to be independent risk factors for OD. The adjusted odds ratio of live birth rate per OPU cycle were similar in different oocyte degeneration rate subgroups. The ongoing pregnancy/LBR per transfer in FET cycles was not significantly different between OD group and non-OD groups (38.8% vs 43.9%, P=0.439). The cumulative LBR per OPU cycle was also comparable between OD and non-OD group (63.4% vs 64.8%, P=0.760).ConclusionThe results provide cycle-based evidence that the presence of oocyte degeneration after ICSI is not an indicator for predicting the cumulative live birth rate per OPU cycle in young women.

Obstetric and neonatal outcomes after frozen-thawed embryos transfer with laser-assisted hatching: a retrospective cohort study.

To ascertain if assisted hatching (AH) increases the risk of placenta-associated diseases and perinatal outcomes after frozen-thawed cleavage-stage embryo transfer. We retrospectively evaluated 924 women who conceived with frozen-thawed cleavage-stage embryos transfer with (n = 390) or without (n = 534) laser-AH between 2013 and 2015. Data were obtained from the database on in vitro fertilization (IVF) patients in Shanghai First Maternity and Infant Hospital. We assessed neonatal (preterm birth, low birthweight, fetal macrosomia, stillbirth) and obstetric (miscarriage, ectopic pregnancy, post-term pregnancy, gestational diabetes (GDM), preeclampsia, intrahepatic cholestasis (ICP), placenta previa, placental abruption, premature rupture of membranes) outcomes. In twins, the median birthweight was lower in the AH group than that in the control group, and the prevalence of low birthweight (< 2500g) was significantly higher in the AH group; after adjusting for maternal age, body mass index, mode of fertilization, and parity, no significant difference was found. In twins, no significant difference was detected in the prevalence of stillbirth or preterm pregnancy. In singleton births, there was no significant difference in the prevalence of low birthweight, macrosomia, preterm pregnancy or post-term pregnancy between the two groups. In singletons and twins, there were no significant differences in the prevalence of miscarriage, ectopic pregnancy, preeclampsia, GDM, ICP, or placenta abruption between the two groups. AH is a relatively safe method and our study provides important information for using this method in carefully selected patients.

P–755 Perinatal outcomes following Day–4 embryo transfer compared to Day–2, Day–3 and Day–5 embryo transfer: an analysis of 56,346 singleton live births

Abstract Study question Are perinatal outcomes of singleton live births following Day–4 embryo transfer (ET) different to Day–2, Day–3 and Day–5 ET? Summary answer Perinatal outcomes of singleton live births following Day–4 ET are similar with those following Day–2, Day–3 and Day–5 ET. What is known already The morula represents a critical stage in preimplantation embryo development, but the usage of morula transfer on Day–4 has received little attention. Recent work from our group suggested that live birth rates following Day–4 ET appear higher than cleavage-stage ET, but lower than blastocyst ET. Therefore, Day–4 appears an alternative day to perform ET, offering the benefits of extended culture for embryo selection, but with shorter in-vitro culture exposure, as well as improving flexibility and planning in the IVF Clinic. However, there are extremely limited data available on the perinatal outcomes after Day–4 ET compared to cleavage-stage and blastocyst ET. Study design, size, duration Retrospective cohort study using data from the anonymised dataset of the Human Fertilisation and Embryology Authority (HFEA) in the UK between 2000 and 2016. Data from singleton live births of women undergoing their first IVF/ICSI cycle were analysed to compare perinatal outcomes after fresh Day–2,3,4,5 embryo transfers. Participants/materials, setting, methods Births resulting from the first, fresh, autologous, stimulated, non-PGT cycles, with full data, were included. After exclusions, a total 56,346 singleton live births were included in the analysis (17,613 from Day–2 ET, 15,533 from Day–3 ET, 508 from Day–4, 22,692 from Day–5 ET). Binary/multinomial logistic regression analysis was performed to adjust for important cofounders. Adjusted odds ratios (aORs) and 95% confidence intervals (95%CI) were calculated. The level of significance was set at &amp;lt; 0.05. Main results and the role of chance The probabilities of birth at full-term (FT) and normal birthweight (NBW) after Day–4 transfer (FT 90.4%; NBW 84.6%) were similar to Day–2 (FT 89.7%, aOR 0.994, [0.734–1.344]; NBW 81.9%, aOR 0.881, [0.708–1.096]), Day–3 (FT 90.2%, aOR 1.026, [0.760–1.386]; NBW 82.4%, aOR 0.894, [0.719–1.111]) and Day–5 transfer (FT 90.4%, aOR 1.001, [0.743–1.350]; NBW 83.7%, aOR 0.920, [0.741–1.142]). The probabilities of preterm birth (PTB) and very preterm birth (VPTB) after Day–4 transfer (PTB 9.3%; VPTB 0.4%) were similar to Day–2 (PTB 9.5%; aOR=0.952; VPTB 0.8%; aOR=2.172), Day–3 (PTB 9.0%, aOR=0.920; VPTB 0.9%, aOR=2.174), and Day–5 transfer (PTB 8.8%; aOR=0.955; VPTB 0.8%, aOR=1.956). The probabilities of very-low birthweight (VLBW), low birthweight (LBW), high birthweight (HBW) and very-high birthweight (VHBW) after Day–4 transfer (VLBW 0.9%, LBW 7.9%, HBW 6.3%, VHBW 0.3%) were similar to Day–2 (VLBW 1.8%, aOR=1.827; LBW 8.0%, aOR=1.015; HBW 8.1%, aOR=1.174; VHBW 0.2%, aOR=0.590), Day–3 (VLBW 1.8%, aOR=1.788; LBW 7.4%, aOR=0.927; HBW 8.3%, aOR=1.256; VHBW 0.2%, aOR=0.503) and Day–5 transfer (VLBW 1.6%, aOR=1.782; LBW 6.9%, aOR=0.894; HBW 7.5%, aOR=1.215; VHBW 0.2%, aOR=0.796). The probability of having a female baby after Day–4 transfer (51.6%) was similar to Day–2 (49.2%, aOR 0.940), Day–3 (49.3%, aOR 0.931) and Day–5 transfer (48.3%, aOR 0.869). Limitations, reasons for caution The study is limited by its retrospective nature, the inability to adjust for additional confounders and the small number of singleton births after Day–4 ET. It is not known how Day–4 ET was decided. The incidence of congenital abnormalities was not analysed due to incomplete registration in the dataset. Wider implications of the findings: Perinatal outcomes of singleton live births following Day–4 ET are similar with those following Day–2, Day–3 and Day–5 ET, suggesting that morula transfer is equally safe as cleavage-stage and blastocyst transfer. Data on a larger number of live births from well-designed RCTs are required to confirm these findings. Trial registration number Not applicable

P–609 The chances of one live birth rates after first ART cycle in minimal stimulation cycle IVF with letrozole only and natural cycle IVF

Abstract Study question Are one live birth rates (LBRs) similar in minimal stimulation cycle IVF with letrozole only and natural cycle IVF for the first ART cycle? Summary answer LBRs after first ART cycle in minimal stimulation cycle IVF with letrozole only are superior to natural cycle IVF. What is known already The addition of letrozole to gonadotropins in ovarian stimulation (OS) may reduce the risk of OHSS, but there is no significant difference were reported in ongoing pregnancy rate or number of oocytes retrieved in the letrozole + FSH group compared to the FSH only. No differences were also reported in clinical pregnancy rates or number of mature oocytes in the additional of letrozole in an GnRH antagonist protocol group compared to the GnRH antagonist group. There are no previous study comparing LBRs after first ART cycle in minimal stimulation cycle IVF with letrozole and natural cycle IVF. Study design, size, duration Data for this retrospective cohort study were obtained 643 women, 30–39 years of age started their first ART cycle at one private fertility clinic between January 2016- December 2019. Participants/materials, setting, methods A total of 643 women were scheduled their first oocyte retrieval cycle. 118 women started with letrozole (LE) and 525 women started natural cycle (NC). The main strategy for OS in our center is minimal stimulation and natural cycle IVF. Patients consulted with gynecologists to determine their treatment plan based on patients’ preference or their menstrual cycle. All pregnancies generated from oocyte retrieval during the first IVF cycle including fresh and frozen-thaw cycles were registered. Main results and the role of chance The number of retrieved oocytes and the normal fertilization rates were significantly higher in the LE than NC (4.4 vs 3.4, 77.6% vs 71.1%), p &amp;lt; 0.05 respectively). There was no significant difference in the clinical pregnancy rates (CPRs) per embryo transfer (ET) (fresh cleavage stage ET: 32.9% vs 28.0%, frozen-thaw blastocyst ET: 39.4% vs 44.9% ns). However, the CPRs and LBRs per oocyte retrieval (OR) were significantly higher in the LE group (39.0% vs 28.6, 33.9% vs 21.9%, p &amp;lt; 0.05 respectively). In a subsequent regression analyses, LBRs per OR of LE was significantly higher than NC as well. (adjusted OR = 1.63 (95% CI: 1.02–2.58, p = 0.041). Limitations, reasons for caution The strength of the present study was the use of a large cohort of women who underwent minimal stimulation IVF with letrozole only. Although our results are promising, limited by retrospective cohort study. These interpretations prompted the need for a perspective cohort study to evaluate the efficacy of letrozole. Wider implications of the findings: When comparing minimal stimulation IVF with letrozole only and natural cycle IVF, we found significantly higher LBRs per OR in minimal stimulation IVF with letrozole only, despite similar CPRs per ET. Trial registration number none

P–281 Is it worth to go to blastocyst when there are less than 4 embryos on day 3?

Abstract Study question Are pregnancy rates similar with blastocyst transfer compared to D3 transfer for patient with a poor embryo yield. Summary answer In poor prognosis patients, more D3 embryos are needed to result in similar outcome compared to single blastocyst and it increases the multiple pregnancy risk. What is known already Good prognosis patients benefit from a blastocyst transfer rather than cleavage-stage embryo because day 3 morphology has limited predictive value for subsequent developmental. A Cochrane meta-analysis in 2016 found a higher live birth rate per transfer in the blastocyst group compared to cleavage-stage and no difference in miscarriage and multiple pregnancies. However, in unselected patients, studies have yielded conflicting results and especially in poor prognosis patients at risk of transfer cancellation. A threshold of four good embryos on the third day has been previously correlated with blastocyst yield and live birth rate compared with cleavage-stage embryo transfer. Study design, size, duration We analyzed the outcome of 1115 cycles with less than 4 embryos during 2019–2020 and compared the results between two groups of D3 and D5 transfers. Participants/materials, setting, methods Amongst 1115 study cycles, in 691 cycles a D3 transfer was performed and in 424 cycles a D5 transfer was performed. We compared transfer cancellation rates, mean number of transferred embryos and ongoing pregnancy rates between the two groups and also in subgroups with female age &amp;lt;37 and female age &amp;gt;37. The statistical analyses were done by Chi square and t-test for paired samples. Main results and the role of chance In the overall study population, the mean female age was 36.3 ± 4.3 years, the mean number of obtained embryos was 2.4 ± 1.0, the mean number of transferred embryos was 1.4 ± 0.8. 17.2% of the cycles resulted in transfer cancellation (6.2% in D3 transfer group and 35.0% in D5 transfer group). After D3 transfer the ongoing pregnancy rate (OPR) per transfer was 21.5% compared to 39.7% in D5 transfers (p &amp;lt; 0.05). A similar pattern was observed in subgroups of age &amp;lt;37 years and &amp;gt;37 years with OPR per transfer significantly higher when D5 transfer was performed. Notably more embryos were transferred on D3 compared to D5 (mean number 1.4 for D3 and 1 for D5). Nonetheless, OPR were similar per cycle in both groups and subgroups of different ages. Limitations, reasons for caution A prospective randomized controlled trial is needed to confirm these results that are consistent with previously reports on retrospective and observational studies. Wider implications of the findings: In poor prognosis patients with low embryo yield, D3 and D5 transfers result in similar OPR per cycle. Transferring at blastocyst stage is not inferior to D3, despite the high cancellation rate, and appears safer permitting a single embryo transfer to avoid multiple pregnancy. Trial registration number Not applicable

P–775 Obstetric and perinatal outcomes of singleton pregnancies after blastocyst-stage embryo transfer: a systematic review and cumulative meta-analysis

Abstract Study question Are obstetric/perinatal outcomes different in singleton pregnancies following blastocyst-stage embryo transfer when compared to cleavage-stage embryo transfer and have results changed over time? Summary answer Pregnancies following blastocyst are consistently associated with higher risk of large for gestational age and lower risk of small for gestational age babies What is known already Extended embryo culture to blastocyst-stage is widely used to select best embryos in in vitro fertilisation (IVF) cycles to improve pregnancy rates. Transfer of blastocyst-stage embryos is increasing with this being the default strategy in most clinics. As blastocysts are kept in culture until day 5, 6 or 7 after oocyte fertilisation, there are suggestions that longer exposure to culture media may have a negative impact on pregnancy outcomes. More recent primary studies have challenged some of the initial findings. We therefore conducted an updated systematic review and cumulative meta-analysis (CMA) to examine if these results have changed over time. Study design, size, duration Systematic review of studies published between 1980 and 2020, followed by aggregated meta-analysis and CMA to track the accumulation of evidence over the period of time. Exposed group: singleton pregnancies following blastocyst transfer. Non-exposed group: singleton pregnancies following cleavage-stage transfer. Sub-group analyses were conducted on fresh and frozen-thawed embryo transfers. Perinatal (categories of preterm birth and birth weight) and obstetric outcomes (hypertensive disorders of pregnancy, gestational diabetes, c-section, placental anomalies) were compared between the groups. Participants/materials, setting, methods Medline, EMBASE, CINHAL, Web of Science, Cochrane Central Register of Clinical Trials and International Clinical Trials Registry Platform databases were searched. Relevant journals were searched for advance access publications. Critical Appraisal Skills Programme (CASP) checklists were used to assess study quality. Two independent reviewers extracted data in 2 × 2 tables. Aggregated and CMA were performed using Comprehensive Meta-Analysis software. Risk ratio (RR) with 95% confidence interval (CI) were calculated. Main results and the role of chance A total of 33 observational studies were included (n = 574,756 singleton pregnancies). Pregnancies following blastocyst-stage embryo transfer are associated with a higher risk of preterm birth (PTB) (RR 1.09; 95% CI 1.01–1.17), very preterm birth (VPTB) (RR 1.15; 95% CI 1.07–1.24), large for gestational age (LGA) babies (RR 1.13; 95% CI 1.08–1.19), c-section (RR 1.05; 95% CI 1.02–1.09), and with a lower risk of small for gestational age (SGA) babies (RR 0.86; 95% CI 0.81–0.93) as compared to singleton pregnancies following cleavage-stage embryo transfer. These findings were maintained in both fresh and frozen-thawed sub-groups for LGA and SGA. PTB was not significantly different in both sub-group analyses. The risk of VPTB was higher after blastocyst-stage embryo transfer only in the sub-group analysis of fresh embryo transfers (RR 1.17; 95% CI 1.09–1.27) and that of c-section only in the frozen-thawed sub-group (RR 1.08; 95% CI 1.04–1.12). No other statistically significant differences for the other outcomes were noted. The CMA suggests that for SGA and LGA subsequent studies have increased the precision of the point estimate with no change in the direction or magnitude of the treatment effect since 2014. Limitations, reasons for caution This analysis was constrained by the intrinsic limitations of observational studies with some of them receiving a CASP score &amp;lt; 10. Adjustment for confounders was not possible and a high degree of clinical and statistical heterogeneity was noted among studies. Wider implications of the findings: Blastocyst is associated with a higher risk of LGA and a lower risk of SGA with a stable body of evidence since 2014. We may need to revisit the default position of extending embryo culture and individualise care, until further high-quality data from individual-patient-data of large registries are available. Trial registration number Not applicable

P-767 Cumulative live birth rate after IVF - trend over time and the impact of blastocyst culture and vitrification

Abstract Study question Has cumulative live birth rate (CLBR) improved over time and which factors are associated with such an improvement? Summary answer During 2007-2017, CLBR per oocyte aspiration increased significantly (27.0 % to 36.3 %), in parallel with an increase in blastocyst transfer and cryopreservation by vitrification. What is known already While it has been shown that live birth rate (LBR) per embryo transfer (ET) is higher for fresh blastocyst than for fresh cleavage stage embryo transfer, CLBR per oocyte aspiration, including one fresh ET and all subsequent frozen embryo transfers (FET), does not seem to differ between the two culture strategies. Study design, size, duration STUDY DESIGN, SIZE, DURATION: National register study including all oocyte aspirations performed in Sweden 2007-2017, n = 124 700. Donation cycles excluded. Participants/materials, setting, methods Data were retrieved from the Swedish National Registry of Assisted Reproduction (Q-IVF). CLBR was defined as the number of deliveries with at least one live birth resulting from one oocyte aspiration, including all fresh and/or frozen embryo transfers within one year. The delivery of a singleton, twin, or other multiples was registered as one delivery. Cryopreservation of cleavage stage embryos was performed by slow freezing and of blastocyst by vitrification. Main results and the role of chance Overall, the CLBR per oocyte aspiration increased significantly during the study period, from 27.0 % to 36.3 % (OR 1.039, 95% CI 1.035-1.043) and from 30.0 % to 43.3 % if at least one ET was performed (AOR 1.055, 95% CI 1.050-1.059). The increase in CLBR was independent of maternal age, number of oocytes retrieved and number of previous IVF live births. The CLBR for women &amp;lt; 35 years and ≥ 35 years both increased significantly, following the same pattern. During the study period a substantially increasing number of blastocyst transfers were performed, both in fresh and in FET cycles. An important contributor included in the blastocyst strategy, may be the extended culture of the total cohort of embryos, also embryos earlier discarded at early cleavage stages, in order to reach the blastocyst stage. These embryos may contribute to the total number of available blastocysts and thereby increase the chance of a live birth within that oocyte aspiration cycle. Other important predicting factors for live birth, such as number of embryos transferred, could not explain the improvement, on the contrary the single embryo transfer (SET) rate increased with time. Limitations, reasons for caution The retrospective design implicates that other confounders of importance for CLBR can not be ruled out. In addition, some FET cycles might be performed later than one year post oocyte aspiration for the last year (2017) and are thus not included in this study. Wider implications of the findings The results suggest that blastocyst transfer, particularly when used in FET cycles and in combination with vitrification, is an important contributor to the improved live birth rates over time. This gives a possibility for fewer oocyte aspirations needed to achieve a live birth and a shortened time to live birth. Trial registration number -

P–767 Cumulative live birth rate after IVF - trend over time and the impact of blastocyst culture and vitrification

Abstract Study question Has cumulative live birth rate (CLBR) improved over time and which factors are associated with such an improvement? Summary answer During 2007–2017, CLBR per oocyte aspiration increased significantly (27.0% to 36.3%), in parallel with an increase in blastocyst transfer and cryopreservation by vitrification. What is known already While it has been shown that live birth rate (LBR) per embryo transfer (ET) is higher for fresh blastocyst than for fresh cleavage stage embryo transfer, CLBR per oocyte aspiration, including one fresh ET and all subsequent frozen embryo transfers (FET), does not seem to differ between the two culture strategies. Study design, size, duration STUDY DESIGN, SIZE, DURATION: National register study including all oocyte aspirations performed in Sweden 2007–2017, n = 124 700. Donation cycles excluded. Participants/materials, setting, methods Data were retrieved from the Swedish National Registry of Assisted Reproduction (Q-IVF). CLBR was defined as the number of deliveries with at least one live birth resulting from one oocyte aspiration, including all fresh and/or frozen embryo transfers within one year. The delivery of a singleton, twin, or other multiples was registered as one delivery. Cryopreservation of cleavage stage embryos was performed by slow freezing and of blastocyst by vitrification. Main results and the role of chance Overall, the CLBR per oocyte aspiration increased significantly during the study period, from 27.0% to 36.3% (OR 1.039, 95% CI 1.035–1.043) and from 30.0% to 43.3% if at least one ET was performed (AOR 1.055, 95% CI 1.050–1.059). The increase in CLBR was independent of maternal age, number of oocytes retrieved and number of previous IVF live births. The CLBR for women &amp;lt;35 years and ≥ 35 years both increased significantly, following the same pattern. During the study period a substantially increasing number of blastocyst transfers were performed, both in fresh and in FET cycles. An important contributor included in the blastocyst strategy, may be the extended culture of the total cohort of embryos, also embryos earlier discarded at early cleavage stages, in order to reach the blastocyst stage. These embryos may contribute to the total number of available blastocysts and thereby increase the chance of a live birth within that oocyte aspiration cycle. Other important predicting factors for live birth, such as number of embryos transferred, could not explain the improvement, on the contrary the single embryo transfer (SET) rate increased with time. Limitations, reasons for caution The retrospective design implicates that other confounders of importance for CLBR can not be ruled out. In addition, some FET cycles might be performed later than one year post oocyte aspiration for the last year (2017) and are thus not included in this study. Wider implications of the findings: The results suggest that blastocyst transfer, particularly when used in FET cycles and in combination with vitrification, is an important contributor to the improved live birth rates over time. This gives a possibility for fewer oocyte aspirations needed to achieve a live birth and a shortened time to live birth. Trial registration number -

P–791 Comparison of the live birth rate after single embryo transfer in fresh versus frozen cycle: no evidence to support routine freeze-all strategy

Abstract Study question Is the treatment outcome compromised after superovulation for fresh IVF/ICSI in comparison to frozen cycle with spontaneous ovulation and luteal support with progesterone? Summary answer Live birth rate (LBR) is dependent on embryo quality both in the fresh and frozen cycles with no sign of harmful effect of the superovulation. What is known already Freeze-all strategy has been advocated in recent years based on the assumption that luteal phase after superovulation is not optimal for embryo implantation. The effects of variable hormonal treatments, given in association with ART, on the endometrium, are still largely unknown. Therefore, more data is needed in order to optimize the treatment policies. Study design, size, duration This is an observational retrospective single-center cohort study. Data were collected from Oulu University Hospital’s ART-database including a total of 5647 single embryo transfer cycles from years 1995–2020. Patients stimulated with long agonist protocol for IVF/ICSI and day 2–3 transfer were included. Frozen embryo transfer was performed in a natural cycle with an ovulation test used for timing of transfer. Luteal support with progesterone was given for two weeks in all cycles. Participants/materials, setting, methods There were 3053 IVF/ICSI fresh cycles (2237 top and 816 N-top) and 2594 frozen cycles (806 top and 1788 N-top). The main outcome measure was LBR compared between fresh and frozen cycles when either a top or a N-top embryo was transferred. As a secondary outcome, clinical pregnancy rate was investigated. Data on the age and body mass index (BMI) of the patients was available. Student’s T-test was used to compare continuous variables. Main results and the role of chance The groups did not differ regarding the age and BMI of the patients. After the transfer of a top quality embryo the clinical pregnancy rate (35.4 vs. 30.8%; p &amp;lt; 0.05) and LBR (29.4 vs. 25.5%; p not significant) was slightly higher in the fresh cycle. After the transfer of a N-top quality embryo the clinical pregnancy rate (19.9 vs. 19.4%) and LBR (15.9 vs. 15.4%) were similar both in the fresh and frozen cycles. Limitations, reasons for caution This study only represents cleavage stage embryo transfers, and all FETs were performed in a natural cycle. In a retrospective study there may also be residual confounding that could not be excluded. Wider implications of the findings: This study provides further evidence that treatment outcome regarding LBR is not affected by superovulation therapy. Hence, the use of freeze-all strategy is warranted only in cases with a risk of ovarian hyperstimulation syndrome. Trial registration number Not applicable

P–146 Differential impact of three embryo culture media for IVF on in vitro development and perinatal outcome: a single-center RCT

Abstract Study question This report provides updated data from an RCT determining which embryo culture medium yields optimal IVF outcomes. Summary answer Embryo culture systems used for IVF differentially affected preimplantation development and resultant obstetric and perinatal outcomes, including birthweights of live-born singletons. What is known already Currently, multiple embryo culture medium systems are in use for IVF, raising questions regarding which is optimal. However, the ability of a medium to yield preimplantation embryos is not necessarily indicative of embryo viability. For example, supplementation of medium with serum was commonly used to increase animal blastocyst yields, but this impaired embryonic, fetal, and offspring health. In humans, medium composition and culture duration can influence IVF efficacy and offspring phenotype. Given the importance of culture systems in determining clinical outcomes, existing data regarding differential culture system impacts are insufficient and additional well-designed studies are required. Study design, size, duration Between February 2016 and August 2017, 795 couples undergoing their first autologous clinical IVF cycle and freeze-all strategy were recruited. Participants were randomized via computer-generated tables into three groups. Following standard oocyte retrieval and IVF/ICSI procedures, embryos were cultured using three different culture media, G1 Plus/G2 Plus (G1/G2; Vitrolife), Global Total (GT; LifeGlobal), or Sequential Cleav/Sequential Blast (SC/SB; Origio). Thirty-eight patients exhibiting no 2PN oocytes following insemination or those undergoing fresh embryo transfers were excluded. Participants/materials, setting, methods For patients yielding a single good-quality cleavage-stage (day–2 or day–3) embryo, that cleavage-stage embryo was vitrified. For patients yielding two or more good-quality cleavage-stage embryos, two or less good-quality cleavage-stage embryos were vitrified. The culture period of the remaining embryos was extended, and all good-quality blastocyst-stage (day–5 or day–6) embryos were vitrified. This report presents data for vitrified embryo transfer performed until the end of December 2020. Main results and the role of chance The mean per-cycle vitrified embryo yield (± SD) was comparable between groups for cleavage-stage embryos, but significantly different for blastocyst-stage embryos (G1/G2: 1.69 ± 2.2, GT: 2.53 ± 3.01, SC/SB: 2.04 ± 2.42; P = 0.001). Following vitrified cleavage- or blastocyst-stage embryo transfers, biochemical pregnancy rates were significantly different between groups (G1/G2: 55.6%, GT: 59.1%, SC/SB: 46.2%; P = 0.011). Furthermore, a between-group trend towards different live birth rates was observed (G1/G2: 41.7%, GT: 42.1%, SC/SB: 33.1%; P = 0.063). Of 382 live births, data for first-borns (n = 323; 295 singletons and 14 twin-pairs) are reported here. Perinatal data did not differ significantly between groups for both cleavage- and blastocyst-stage embryo transfers, including gestational age- and gender-adjusted singleton birthweight (z-score). Following multiple linear regression (including selected covariates), adjusted mean singleton birthweights were significantly lower in the G1/G2 and GT groups than in the SC/SB group (by 131 g; P = 0.011 and 110 g; P = 0.032, respectively) and tended to be lower for cleavage-stage embryo transfers than for blastocyst-stage embryo transfers (by 102 g; P = 0.053). Limitations, reasons for caution A larger cohort size and longer-term follow-up are required to verify and further elucidate the impact of embryo culture methods on child health. Such studies will raise awareness regarding the sensitivity of in vitro-cultured human embryos to their environment, ultimately resulting in practices that decrease IVF risks to offspring. Wider implications of the findings: Pregnancy outcome of the medium yielding fewer blastocysts was comparable or superior to that of other media, highlighting the importance of differentiating between the ability to support preimplantation development versus the ability to yield viable embryos. Embryo culture medium had a greater impact than embryo transfer stage on live birthweight. Trial registration number UMIN000020910

O-110 A randomised, controlled, assessor-blind trial assessing clinical outcomes of individualised dosing with follitropin delta in Asian IVF/ICSI patients

Abstract Study question To evaluate the efficacy and safety of individualised dosing with follitropin delta versus conventional dosing with follitropin alfa in an Asian population undergoing ovarian stimulation. Summary answer Individualised dosing with follitropin delta results in significantly higher live birth rate and fewer early OHSS and/or preventive interventions compared to conventional follitropin alfa dosing. What is known already Previous randomised controlled trials conducted in Europe, North- and South America mainly including Caucasian IVF/ICSI patients as well as in Japan have demonstrated that ovarian stimulation with the individualised follitropin delta dosing regimen based on serum AMH level and body weight modulated the ovarian response and reduced the risk of OHSS without compromising pregnancy and live birth rates. Study design, size, duration Randomised, controlled, assessor-blind trial conducted in 1,009 Asian patients from mainland China, South Korea, Vietnam and Taiwan, undergoing their first IVF/ICSI cycle. Randomisation was stratified by age (&amp;lt;35, 35-37, 38-40 years). The primary endpoint was ongoing pregnancy assessed 10-11 weeks after transfer (non-inferiority limit -10.0%; analysis adjusted for age strata). Patients &amp;lt;35 years underwent single embryo transfer if a good-quality embryo was available, otherwise double embryo transfer. Patients ≥35 years underwent double embryo transfer. Participants/materials, setting, methods Follitropin delta (Rekovelle, Ferring Pharmaceuticals) daily treatment consisted of a fixed dose individualised according to each patient’s initial AMH level (&amp;lt;15 pmol/L: 12 μg; ≥15 pmol/L: 0.19 to 0.10 μg/kg; min-max 6-12 μg) and body weight. Follitropin alfa (Gonal-f, Merck Serono) dose was 150 IU/day for the first five days with subsequent potential dose adjustments according to individual response. A GnRH antagonist protocol was applied. OHSS was classified based on Golan’s system. Main results and the role of chance The ongoing pregnancy rate was 31.3% with follitropin delta and 25.7% with follitropin alfa (adjusted difference 5.4% [95% CI: -0.2%; 11.0%]). The live birth rate was significantly higher at 31.3% with follitropin delta compared to 24.7% with follitropin alfa (adjusted difference 6.4% [95% CI: 0.9%; 11.9%]; p &amp;lt; 0.05). Live birth rates per age stratum were as follows for follitropin delta and follitropin alfa; &amp;lt;35 years: 31.0% versus 25.0%, 3537 years: 35.3% versus 26.7%, 38-40 years: 20.0% versus 14.3%. Early OHSS risk, evaluated as the incidence of early OHSS and/or preventive interventions, was significantly (p &amp;lt; 0.01) reduced from 9.6% with follitropin alfa to 5.0% with follitropin delta. The number of oocytes was 10.0±6.1 with follitropin delta and 12.4±7.3 with follitropin alfa. Individualised follitropin delta dosing compared to conventional follitropin alfa dosing resulted in 2 more oocytes (9.6±5.3 versus 7.6±3.5) in potential low responders (AMH &amp;lt;15 pmol/L) and 3 fewer oocytes (10.1±6.3 versus 13.8±7.5) in potential high responders (AMH ≥15 pmol/L). Among patients with AMH ≥15 pmol/L, excessive response occurred less frequently with individualised than conventional dosing (≥15 oocytes: 20.2% versus 39.1%; ≥20 oocytes: 6.7% versus 18.5%). Total gonadotropin dose was reduced from 109.9±32.9 μg with follitropin alfa to 77.5±24.4 μg with follitropin delta. Limitations, reasons for caution The trial only covered the clinical outcome of one treatment cycle with fresh cleavage-stage embryo transfers. Wider implications of the findings The present trial implies that in addition to reducing the early OHSS risk, individualised dosing has the potential to improve the take-home baby rate in fresh cycles across all ages and with a lower gonadotropin consumption. The benefits in outcomes appear to be explained by the modulation of ovarian response. Trial registration number NCT03296527

P–155 Oocyte recovery 39 hours (from 39h to 41h) after administration of follicular maturation trigger does not affect clinical results

Abstract Study question What is the clinical outcome of oocytes recovered after 39 hours from ovulation inducing drug administration? Summary answer Oocytes obtained after 39 hours from follicular maturation triggering are equally viable to those obtained at the standard time of 36 hrs. What is known already In the clinical setting of ART, ovum pick-up (OPU) is generally performed around 36 hours after the administration of ovulation inducing drugs (OID). However, there are cases where OPU cannot be performed at this time often due to long operating lists. As the time elapsed between the administration of ovulation inducing drugs and OPU becomes longer, there is a concern about time-related oocyte aging. Nevertheless, there are few reports of clinical results of OPU after 36 hours from OID. Study design, size, duration We conducted a review of 1187 cycles and 1951 patients in which OPU and embryo transfer was performed in 2017–2018. All cycles underwent a ‘freeze-all’ of embryos and the transfer cycle was in the thawed embryo transfer cycle for all cases. Participants/materials, setting, methods The time from the administration of OID to the end of OPU was divided into 36h group and over 39h group and the MII and normal fertilization rate of oocytes obtained from OPU after ovarian stimulation were compared. After confirmation of fertilization, the D3 good-quality embryo and the D5 and 6 good-quality blastocyst rates of embryos that continued to be cultured and the pregnancy and miscarriage rates of cleavage-stage embryos and blastocyst transfers were compared. Main results and the role of chance The MII rate in the 36h and &amp;gt;39h groups was 78.1% vs. 80.0%, and the normal fertilization rate was 77.9% vs. 78.1% (ICSI) and 65.4% vs. 67.6% (Conventional-IVF). The D3 good-quality embryo rate (good-quality embryos are embryos with less than 5% fragmentation in 7–9 cells and compaction with more than 50% adhesion between split spheres) was 21.8% vs. 25.3%, the D5 good-quality blastocyst rate (at least 3BB according to Gardner classification) was 33.6% vs. 40.1%, and the D6 good-quality blastocyst rate was 31.1% vs. 37.5%, all of which were not significantly different. The pregnancy rate for cleavage-stage embryo transfer was 26.6% vs. 6.7%, and the miscarriage rate was 25.3% vs. 42.9%, both of which were not significantly different. The pregnancy rate for blastocyst transfer was 45.4% vs. 50.0%, and the miscarriage rate was 22.2% vs. 20.0%, both of which were not significantly different. (The significance difference test was a χ-square test) Limitations, reasons for caution The study was a retrospective study. Wider implications of the findings: Even if OPU is conducted after 36h of the administration of OID, to the extreme range of 39h–41h, oocyte aging does not seem apparent and pregnancy outcomes are similar to the standard time interval of 36 hours. Trial registration number ‘not applicable’

The Birth of first JIPMER “ICSI” Baby

Assisted reproductive techniques are becoming more and more essential for human life in the Society. Worldwide more than 5 million babies were born out of this technology after the birth of first baby Louis Brown and second Durga (India) in 1978. It is a boon for the couple in despair to have a child especially when it is provided by Govt Institutions for the less affordable people of the Society. It is essential to share provider’s experiences and expectations of the public in a fast growing biomedical field like ART. The techniques of IVF and ICSI have undergone a sea change since the initial technique of natural cycles to ovarian hyper stimulation and stem cell research. A 29 year old lady, Type I Diabetic with hirsutism, PCOS, failed IUI underwent ICSI following ovarian stimulation employing antagonist protocol after 8 years of married life. The husband is also diabetic for 13 years and suffered from post-polio residual paralysis and had asthenospermia. Frozen Embryo transfer of cleavage stage embryos was done on 31.7.2019 after endometrial preparation employing HRT. Her β HCG was HCG 387 on 14.8.2019 and intrauterine pregnancy was confirmed by transvaginal scan. Pregnancy and Diabetes were managed with progesterone support and Insulin therapy respectively. An alive male baby was delivered by emergency Caesarean section on 28.3.2020 at 12.34 PM for breech presentation in labour during lockdown for COVID 19. Both mother and baby were discharged home in healthy condition and the baby is one year old at the time of writing this report.

Cumulative live birth rate after IVF: trend over time and the impact of blastocyst culture and vitrification.

STUDY QUESTIONHas cumulative live birth rate (CLBR) improved over time and which factors are associated with such an improvement?SUMMARY ANSWERDuring an 11-year period, 2007–2017, CLBR per oocyte aspiration increased significantly, from 27.0% to 36.3%, in parallel with an increase in blastocyst transfer and cryopreservation by vitrification.WHAT IS KNOWN ALREADYWhile it has been shown that live birth rate (LBR) per embryo transfer (ET) is higher for fresh blastocyst than for fresh cleavage stage embryo transfer, CLBR per oocyte aspiration, including one fresh ET and all subsequent frozen embryo transfers (FET), does not seem to differ between the two culture strategies.STUDY DESIGN, SIZE, DURATIONA national register study including all oocyte aspirations performed in Sweden from 2007 to 2017 (n = 124 700 complete IVF treatment cycles) was carried out. Oocyte donation cycles were excluded.PARTICIPANTS/MATERIALS, SETTING, METHODSData were retrieved from the Swedish National Registry of Assisted Reproduction (Q-IVF) on all oocyte aspirations during the study period where autologous oocytes were used. CLBR was defined as the proportion of deliveries with at least one live birth per oocyte aspiration, including all fresh and/or frozen embryo transfers within 1 year, until one delivery with a live birth or until all embryos were used, whichever occurred first. The delivery of a singleton, twin, or other multiples was registered as one delivery. Cryopreservation of cleavage stage embryos was performed by slow freezing and of blastocyst by vitrification.MAIN RESULTS AND THE ROLE OF CHANCEIn total, 124 700 oocyte aspirations were performed (in 61 313 women), with 65 304 aspirations in women <35 years and 59 396 in women ≥ 35 years, resulting in 38 403 deliveries with live born children. Overall, the CLBR per oocyte aspiration increased significantly during the study period, from 27.0% to 36.3% (odds ratio (OR) 1.039, 95% CI 1.035–1.043) and from 30.0% to 43.3% if at least one ET was performed (adjusted OR 1.055, 95% CI 1.050–1.059). The increase in CLBR was independent of maternal age, number of oocytes retrieved and number of previous IVF live births. The CLBR for women <35 and ≥35 years both increased significantly, following the same pattern. During the study period, a substantially increasing number of blastocyst transfers was performed, both in fresh and in FET cycles. Other important predicting factors for live birth, such as number of embryos transferred, could not explain the improvement. An increased single embryo transfer rate was observed with time.LIMITATIONS, REASONS FOR CAUTIONThe retrospective design implicates that other confounders of importance for CLBR cannot be ruled out. In addition, some FET cycles might be performed later than 1 year post oocyte aspiration for the last year (2017) and are, thus, not included in this study. In addition, no data on ‘dropouts’, i.e. patients that do not continue their treatment despite having cryopreserved embryos, are available, or if this drop-out rate has changed over time.WIDER IMPLICATIONS OF THE FINDINGSThe results suggest that blastocyst transfer, particularly when used in FET cycles and in combination with vitrification, is an important contributor to the improved live birth rates over time. This gives a possibility for a lower number of oocyte aspirations needed to achieve a live birth and a shortened time to live birth.STUDY FUNDING/COMPETING INTERESTSThe study was financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-70940) and by Hjalmar Svensson’s research foundation. None of the authors declares any conflict of interest.

Is there still a role for a cleavage-stage embryo transfer?

ObjectiveTo determine whether pregnancy outcomes are poor or futile when an intended day 5 transfer is converted to a cleavage-stage transfer because of poor embryo development or a lower number of embryos.DesignRetrospective cohort study.SettingAcademic medical center.Patient(s)Women with a limited number of embryos, defined as ≤6 two pronuclear embryos, after in vitro fertilization.Intervention(s)Patients who had a cleavage-stage transfer were age matched with patients who had a day 5 transfer.Main Outcome Measure(s)Live birth rate.Result(s)A total of 146 women were included in the study with 73 women in each group. Cleavage-stage transfer was associated with significantly lower implantation and clinical pregnancy rates compared with those of day 5 transfer. Although the live birth rate of the cleavage-stage transfer group was lower than that of the day 5 transfer group (25% vs. 40%, respectively), the cleavage-stage transfer still resulted in a live birth rate of 25%. A subanalysis comparing women who did and did not achieve live birth after cleavage-stage transfer demonstrated a live birth rate of 27% when at least one grade A embryo was transferred vs. 17% when a lesser quality embryo (grade B or C) was transferred.Conclusion(s)As expected, the live birth rate after cleavage-stage transfer was lower than that after day 5 transfer. However, the live birth rate of cleavage-stage transfer still fell into acceptable practice, >5%, for patients who were otherwise at very high risk of having no day 5 embryo transfer. Extended culture may not be necessary for all patients.

Length of estradiol exposure >100 pg/ml in the follicular phase affects pregnancy outcomes in natural frozen embryo transfer cycles.

Do the length of follicular phase estradiol exposure and the total length of the follicular phase affect pregnancy and live birth outcomes in natural frozen embryo transfer (FET) cycles? An estradiol level >100 pg/ml for ≤4 days including the LH surge day is associated with worse pregnancy and live birth outcomes; however, the total length of the follicular phase is not associated with pregnancy and live birth outcomes. An estradiol level that increases above 100 pg/ml and continues to increase is indicative of the selection and development of a dominant follicle. In programmed FET cycles, a limited duration of follicular phase estradiol of <9 days results in worse pregnancy rates, but a prolonged exposure to follicular phase estradiol for up to 4 weeks does not affect pregnancy outcomes. It is unknown how follicular phase characteristics affect pregnancy outcomes in natural FET cycles. This retrospective cohort study included infertile patients in an academic hospital setting who underwent their first natural frozen autologous Day-5 embryo transfer cycle in our IVF clinic between 01 January 2013 and 31 December 2018. Donor oocyte and gestational carrier cycles were excluded. The primary outcomes of this study were pregnancy and live birth rates. Patients were stratified into two groups based on the cohorts' median number of days from the estradiol level of >100 pg/ml before the LH surge: Group 1 (≤4 days; n = 1052 patients) and Group 2 (>4 days; n = 839 patients). Additionally, patients were stratified into two groups based on the cohorts' median cycle day of LH surge: Group 1 (follicular length ≤15 days; n = 1287 patients) and Group 2 (follicular length >15 days; n = 1071 patients). A subgroup analysis of preimplantation genetic testing for aneuploidies (PGT-A) embryo transfer cycles was performed. Logistic regression analysis, adjusted a priori for patient age, number of embryos transferred, and use of PGT-A, was used to estimate the odds ratio (OR) with a 95% CI. In the length of elevated estradiol analysis, the pregnancy rate per embryo transfer was statistically significantly lower in patients with an elevated estradiol to surge of ≤4 days (65.6%) compared to patients with an elevated estradiol to surge of >4 days (70.9%; OR 1.30 (95% CI 1.06-1.58)). The live birth rate per embryo transfer was also statistically significantly lower in patients with an elevated estradiol to surge of ≤4 days (46.6%) compared to patients with an elevated estradiol to surge of >4 days (52.0%; OR 1.23 (95% CI 1.02-1.48)). In the follicular phase length analysis, the pregnancy rate per embryo transfer was similar between patients with a follicular length of ≤15 days (65.4%) and patients with a follicular length of >15 days (69.0%; OR 1.12 (95% CI 0.94-1.33)): the live birth rate was also similar between groups (45.5% vs 51.5%, respectively; OR 1.14 (95% CI 0.97-1.35)). In all analyses, once a pregnancy was achieved, the length of the follicular phase or the length of elevated oestradiol >100 pg/ml no longer affected the pregnancy outcomes. The retrospective design of this study is subject to possible selection bias in regard to which patients at our clinic were recommended to undergo a natural FET compared to a fresh embryo transfer or programmed FET. To decrease the heterogeneity of our study population, we only included patients who had blastocyst embryo transfers; therefore, it is unknown whether similar results would be observed in patients with cleavage-stage embryo transfers. The retrospective nature of the study design did not allow randomized to a specific ovarian stimulation or ovulation trigger protocol. However, all patients were managed with the standardized protocols at a single center, which strengthens the external validity of our results when compared to a study that only evaluates one specific stimulation protocol. Our observations provide cycle-level characteristics that can be applied during a natural FET cycle to help optimize embryo transfer success rates. Physicians should consider the parameter of number of days that oestradiol is >100 pg/ml prior to the LH surge when determining whether to proceed with embryo transfer in a natural cycle. This cycle-specific characteristic may also help to provide an explanation for some failed transfer cycles. Importantly, our findings should not be used to determine whether to recommend a natural or a programmed FET cycle for a patient, but rather, to identify natural FET cycles that are not optimal to proceed with embryo transfer. No financial support, funding, or services were obtained for this study. The authors do not report any potential conflicts of interest. N/A.

Ovarian Hyperstimulation Syndrome Is Associated with a High Secondary Sex Ratio in Fresh IVF Cycles with Cleavage-Stage Embryo Transfer: Results for a Cohort Study.

The sex ratio at birth is defined as the secondary sex ratio (SSR). Ovarian hyperstimulation syndrome (OHSS) is a serious and iatrogenic complication associated with controlled ovarian stimulation (COS) during assisted reproductive technology (ART) treatments. It has been hypothesized that the human SSR is partially controlled by parental hormone levels around the time of conception. Given the aberrant hormonal profiles observed in patients with OHSS, this retrospective study was designed to evaluate the impact of OHSS on the SSR. In this study, all included patients were divided into 3 groups: non-OHSS (n=2777), mild OHSS (n=644), and moderate OHSS (n=334). Our results showed that the overall SSR for the study population was 1.033. The SSR was significantly increased in patients with moderate OHSS (1.336) compared to non-OHSS patients (1.002) (p=0.048). Subgroup analyses showed that increases in the SSR in patients with moderate OHSS were observed in the IVF group (1.323 vs 1.052; p=0.043), but not in the ICSI groups (1.021 vs 0.866; p=0.732). In addition, the elevated serum estradiol (E2) and progesterone (P4) levels in OHSS patients were not associated with SSR. In this study, for the first time, we report that a high SSR is associated with OHSS in patients who received fresh IVF treatments. The increases in SSR in OHSS patients are not attributed to the high serum E2 and P4 levels. Our findings may make both ART clinicians and patients more aware of the influences of ART treatments on the SSR and allow clinicians to counsel patients more appropriately.

Effects of Early Cumulus Cell Removal on Treatment Outcomes in Patients Undergoing In Vitro Fertilization: A Retrospective Cohort Study.

BackgroundEarly cumulus cell removal combined with early rescue intracytoplasmic sperm injection (ICSI) has been widely practiced in many in vitro fertilization (IVF) centers in China in order to avoid total fertilization failure. However, uncertainty remains whether the pregnancy and neonatal outcomes are associated with early cumulus cell removal.ObjectivesTo investigate if early cumulus cell removal alone after 4 hours co-incubation of gametes (4 h group), has detrimental effect on the pregnancy and neonatal outcomes in patients undergoing IVF, through a comparison with conventional cumulus cell removal after 20 hours of insemination (20 h group).MethodsThis retrospective cohort study included 1784 patients who underwent their first fresh cleavage stage embryo transfer at the Centre for Assisted Reproduction of Shanghai First Maternity and Infant Hospital from June 2016 to December 2018 (4 h group, n=570; 20 h group, n=1214). A logistic regression analysis was performed to examine the independent association between early cumulus cell removal and pregnancy outcomes after adjustment for potential confounders. The neonatal outcomes between the two groups were compared.ResultsWhen compared with the 20 h group, the 4 h group had similar pregnancy outcomes, including rates for biochemical pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage, ectopic pregnancy, multiple pregnancy, live birth. There were 1073 infants delivered after embryo transfer (4 h group, n=337; 20 h group, n=736). Outcomes in both groups were similar for both singleton and twin gestations, including preterm birth rate and very preterm birth rate, mean birth weight, mean gestational age, sex ratio at birth and rate of congenital birth defects. In addition, findings pertaining to singleton gestations were also similar in the two groups for Z-scores (gestational age- and sex-adjusted birth weight), rates of small for gestational age, very small for gestational age, large for gestational age and very large for gestational age infants.ConclusionsIn this study early cumulus cell removal alone was not associated with adverse pregnancy and neonatal outcomes. From this perspective, early cumulus cell removal to assess for a potential early rescue ICSI is therefore considered to be a safe option in patients undergoing IVF.