Outcome comparisons of controlled ovarian hyperstimulation protocols in adenomyosis patients: a real-world retrospective cohort study

The objective was to investigate whether there are differences in cumulative live birth rate, cumulative clinical pregnancy rate, or perinatal outcomes after delaying ICSI timing. The design was a retrospective cohort study at Fertility North in Australia using 1,969 ICSI cycles with different ICSI timings among 1,078 patients from 2017 to 2022. Cumulative outcomes included cumulative live birth and cumulative clinical pregnancy rates per oocyte retrieval cycle. Perinatal outcomes included preterm birth, low/high birthweight, and small/large for gestational age. Binomial logistic regression and multinomial logistic regression were used. Generalised estimating equation (GEE) was incorporated into the logistic regression analyses to account for the cluster effect from patients undergoing multiple retrieval cycles. ICSI timing was grouped into quartiles: Q1(37.1–41.1h, n = 498), Q2(41.2–42.4h, n = 510), Q3(42.5–43.3h, n = 483), and Q4(43.4–46.8h, n = 478). No significant difference was found in cumulative live birth in Q2 (aOR: 0.79, 95%CI: 0.55–1.14), Q3 (0.87, 0.61–1.25), and Q4 (0.86, 0.58–1.27), compared with Q1, respectively. Similarly, there was no significant difference in cumulative clinical pregnancy rate between the four groups. Furthermore, no significant differences were found in preterm birth, low birth weight, high birth weight, small for gestational age, and large for gestational age in Q4, compared to Q1. Delaying ICSI until 46.8 hours post-trigger does not compromise cumulative clinical pregnancy or live birth rates, or increase adverse perinatal risks.

Elective single-embryo transfer in oocyte donation programmes: should it be the rule?

To provide an assessment of pregnancy and live birth probabilities for women presenting for in vitro fertilisation treatment for the first time, when committed in advance to have up to three cycles of treatment in one year. Up to three cycles of in vitro fertilisation within one year, committed in advance. A tertiary referral centre for assisted reproduction. Two hundred and thirty-two women, undergoing a total of 536 cycles of in vitro fertilisation or intracytoplasmic sperm injection between August 1993 and December 1995. Analysis of cumulative clinical pregnancy and live birth rates for women having IVF treatment for the first time and undertaking a three-cycle package, using the life-table approach. Cumulative clinical pregnancy and live birth rates. The cumulative probabilities of clinical pregnancy and live birth after two cycles of treatment were 38.2% and 33.2%, respectively, compared with 54.2% and 48.2%, respectively, after three cycles of treatment. Cumulative clinical pregnancy and live birth rates after three cycles of treatment for women up to the age of 40 years were 57.8% and 51.3%, respectively. Cumulative clinical pregnancy and live birth rates declined with increasing age (P = 0.02 and P= 0.01, respectively). The three-cycle package encourages couples to have multiple treatment cycles, thereby improving their ultimate chances of a live birth. The cumulative clinical pregnancy and live birth rates after such a package provide a more realistic assessment of overall and age-specific success rates after multiple treatment cycles.

Blastocyst versus day-3 embryo transfers: A comparison of fresh and thaw cycle cumulative outcomes

Are cumulative pregnancy rates better if supernumerary embryos are vitrified on Day 5/6 instead of Day 3? The results do not show a significant difference in cumulative pregnancy rates between the Day 3 and Day 5/6 vitrification groups. Pregnancy and live birth rates following IVF or ICSI treatment are higher after extended embryo culture and blastocyst transfer (Day 5/6) compared to cleavage-stage (Day 3) transfer. Cumulative pregnancy rates from one oocyte retrieval (OR) cycle show no significant difference after fresh and frozen embryo transfers, but only one study has used vitrification for the cryopreservation of supernumerary embryos while four studies have used a slow freezing protocol. Our prospective randomized controlled trial was performed in an academic centre between January 2018 and August 2020. Patients were randomized into vitrification Day 3 (n = 80) or Day 5/6 (n = 81) groups. The primary outcome was the cumulative ongoing pregnancy rate (cOPR), considering only the first pregnancy for each couple. The power calculation revealed that 75 patients were required in each group, when assuming a 50% cOPR with four embryo transfers in the vitrification Day 3 group vs two transfers in the vitrification Day 5/6 group. Patients <38 years undergoing their first or second OR cycles were randomized at the start of the first cycle. Up to two cycles were included in the analysis. A fresh embryo transfer was performed on Day 3. Supernumerary embryos (with ≥6 cells, <25% fragmentation, and equal blastomeres) or blastocysts (with expansion grade ≥2 with inner cell mass and trophectoderm score A/B) were vitrified on Day 3 or Day 5/6, respectively, and then transferred at a later date. A time-to-event analysis was performed with the patient's first ongoing pregnancy as the event of interest and the number of embryo transfers as the time component. The statistical comparison was performed by a Cox proportional hazards model. Cumulative costs of vitrification on Day 3 vs Day 5/6 were explored and compared using Mann-Whitney U tests. By December 2021, 233 transfers (96 fresh and 137 frozen) in 77 patients were performed in the vitrification Day 3 group and 201 transfers (88 fresh and 113 frozen) in 77 patients were performed in the vitrification Day 5/6 group. The time-to-event analysis did not show a difference between the two arms with regard to the patient's first ongoing pregnancy as the primary study outcome (hazard ratio [HR] 1.25, 95% CI 0.82; 1.92, P = 0.30). The cumulative ongoing pregnancy rate after eight transfers (from one or two ORs) was 57% in the vitrification Day 3 group vs 58% in the vitrification Day 5/6 group. The median number of embryo transfers until a pregnancy was achieved was five vs four, respectively, in the vitrification Day 3 group vs the Day 5/6 group. Similar results were found for the secondary study outcome, i.e. clinical pregnancy with foetal heart rate (HR 1.19, 95% CI 0.78; 1.80, P = 0.41). The cumulative clinical pregnancy rate (cCPR) after eight embryo transfers was 62% in the vitrification Day 3 group vs 59% in the vitrification Day 5/6 group. The median number of transfers until a pregnancy was achieved was four in both groups. The healthcare consumption pattern differed between the two groups and we observed higher costs for the vitrification Day 3 group compared to the vitrification Day 5/6 group, although these differences were not statistically significant. Although our power calculation revealed that only 75 patients were needed in each study group (β = 0.87, α < 0.05), the numbers were low. Also, different numbers of single and double embryo transfers were performed between the two groups, which may have affected the results. The cost analysis was performed on a subset of the patients and is therefore exploratory. Our study shows no difference in the cumulative pregnancy rate nor costs after fresh and frozen embryo transfers of at most two sequential OR cycles between the Day 3 and Day 5/6 vitrification groups; however, obstetric and perinatal outcomes should be taken into account to determine the best strategy. This study was funded as an investigator-sponsored study of S.D. by Merck nv/sa Belgium, an affiliate of Merck KGaA, Darmstadt, Germany, and by Gedeon Richter Benelux (PA18-0162). The authors declare no conflict of interest related to this study. NCT04196036. 15 January 2018. 15 January 2018.

Advances in cell culture media have led to a shift in in vitro fertilisation (IVF) practice from cleavage stage embryo transfer to blastocyst stage transfer. The rationale for blastocyst transfer is to improve both uterine and embryonic synchronicity and enable self selection of viable embryos, thus resulting in better live birth rates. To determine whether blastocyst stage (day 5 to 6) embryo transfers improve the live birth rate, and other associated outcomes, compared with cleavage stage (day 2 to 3) embryo transfers. We searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library; 2016, Issue 4), MEDLINE, EMBASE, PsycINFO, CINAHL, and Bio extracts from inception to 4th April 2016. We also searched registers of ongoing trials and the reference lists of studies retrieved. We included randomised controlled trials (RCTs) which compared the effectiveness of blastocyst versus cleavage stage transfers. We used standard methodological procedures recommended by Cochrane. Our primary outcomes were live birth and cumulative clinical pregnancy rates. Secondary outcomes were clinical pregnancy, multiple pregnancy, high order pregnancy, miscarriage, failure to transfer embryos, and embryo freezing. We assessed the overall quality of the evidence for the main comparisons using GRADE methods. We included 27 RCTs (4031 couples or women).The live birth rate following fresh transfer was higher in the blastocyst transfer group (odds ratio (OR) 1.48, 95% confidence interval (CI) 1.20 to 1.82; 13 RCTs, 1630 women, I(2) = 45%, low quality evidence) following fresh transfer. This suggests that if 29% of women achieve live birth after fresh cleavage stage transfer, between 32% and 42% would do so after fresh blastocyst stage transfer.There was no evidence of a difference between the groups in rates per couple of cumulative pregnancy following fresh and frozen-thawed transfer after one oocyte retrieval (OR 0.89, 95% CI 0.64 to 1.22; 5 RCTs, 632 women, I(2) = 71%, very low quality evidence).The clinical pregnancy rate was also higher in the blastocyst transfer group, following fresh transfer (OR 1.30, 95% CI 1.14 to 1.47; 27 RCTs, 4031 women, I(2) = 56%, moderate quality evidence). This suggests that if 36% of women achieve clinical pregnancy after fresh cleavage stage transfer, between 39% and 46% would do so after fresh blastocyst stage transfer.There was no evidence of a difference between the groups in rates of multiple pregnancy (OR 1.05, 95% CI 0.83 to 1.33; 19 RCTs, 3019 women, I(2) = 30%, low quality evidence), or miscarriage (OR 1.15, 95% CI 0.88 to 1.50; 18 RCTs, 2917 women, I(2) = 0%, low quality evidence). These data are incomplete as under 70% of studies reported these outcomes.Embryo freezing rates were lower in the blastocyst transfer group (OR 0.48, 95% CI 0.40 to 0.57; 14 RCTs, 2292 women, I(2) = 84%, low quality evidence). This suggests that if 60% of women have embryos frozen after cleavage stage transfer, between 37% and 46% would do so after blastocyst stage transfer. Failure to transfer any embryos was higher in the blastocyst transfer group (OR 2.50, 95% CI 1.76 to 3.55; 17 RCTs, 2577 women, I(2) = 36%, moderate quality evidence). This suggests that if 1% of women have no embryos transferred in (planned) fresh cleavage stage transfer, between 2% and 4% will have no embryos transferred in (planned) fresh blastocyst stage transfer.The evidence was of low quality for most outcomes. The main limitation was serious risk of bias, associated with failure to describe acceptable methods of randomisation, and unclear or high risk of attrition bias. There is low quality evidence for live birth and moderate quality evidence for clinical pregnancy that fresh blastocyst stage transfer is associated with higher rates than fresh cleavage stage transfer. There was no evidence of a difference between the groups in cumulative pregnancy rates derived from fresh and frozen-thawed cycles following a single oocyte retrieval, but the evidence for this outcome was very low quality. Thus, although there is a benefit favouring blastocyst transfer in fresh cycles, it remains unclear whether the day of transfer impacts on cumulative live birth and pregnancy rates. Future RCTs should report rates of live birth, cumulative live birth, and miscarriage to enable couples or women undergoing assisted reproductive technology (ART) and service providers to make well informed decisions on the best treatment option available.

Study QuestionDoes dual trigger in freeze-all in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles improve the cumulative live-birth outcome compared with human chorionic gonadotropin (hCG) trigger?Summary AnswerDual trigger for final follicular maturation improves the cumulative pregnancy and live-birth rates compared with hCG trigger in freeze-all IVF/ICSI cycles.What Is Known AlreadyDual trigger could increase the numbers of oocytes and mature oocytes and improve pregnancy rates.Study Design, Size, DurationThis retrospective cohort analysis included data from 4438 freeze-all IVF/ICSI cycles between January 2012 and December 2017.Participants/Materials, Setting, MethodsWomen aged 20−49 years who underwent ovarian stimulation and oocyte retrieval for autologous IVF/ICSI with a freeze-all policy in our centre were enrolled. Data on number of oocytes retrieved, number of mature oocytes, clinical pregnancy rate, live-birth rate, cumulative pregnancy rate, and cumulative live-birth rate (CLBR) were assessed and compared between patients who underwent a dual trigger and hCG trigger. Multivariate logistic regression was performed to identify and adjust for factors known to independently affect the CLBR.Main Results and the Role of ChanceA total of 4438 IVF/ICSI cycles were analyzed, including 1445 cycles with single hCG trigger and 2993 cycles with dual trigger. The cumulative biochemical pregnancy rate (60.8% vs. 68.1%, P<0.001; odds ratio (OR): 0.727; 95% confidence interval (CI): 0.638–0.828), cumulative clinical pregnancy rate (52.9% vs. 58.5%, P<0.001; OR: 0.796; 95%CI: 0.701–0.903), and CLBR (44.3% vs. 50.5%, P<0.001; OR: 0.781; 95%CI: 0.688–10.886) were all significantly lower in the hCG-trigger group compared with the dual-trigger group. The clinical pregnancy rate (48.2% vs. 58.2%, P=0.002; OR: 0.829; 95%CI: 0.737–0.934) and embryo implantation rate (34.4% vs. 38.9%, P<0.001; OR: 0.823; 95%CI: 0.750–0.903) in each transfer cycle were also significantly lower in the hCG-trigger group compared with the dual-trigger group. After controlling for all potential confounding variables, the trigger method was identified as an independent factor affecting the CLBR. The OR and 95%CI for hCG trigger were 0.780 and 0.641–0.949 (P=0.013).Limitations, Reasons for CautionThe data used to analyse the effect of dual trigger on cumulative pregnancy and live-birth outcomes were retrospective, and the results may thus have been subject to inherent biases. Further prospective randomized controlled trials are required to verify the beneficial effects of dual trigger.Wider Implications of the FindingsDual trigger had a positive effect on CLBRs, suggesting that it could be used as a routine trigger method in freeze-all cycles.Study Funding/Competing Interest(s)This study was supported by grants from National Key Research and Development Program of China (2018YFC1004800), the Natural Science Program of Zhejiang (LY19H040009), the National Natural Science Foundation of China (No. 81601236). No authors have competing interests to declare.

Background The aim of this study is to determine whether infertile couples who are carriers of chromosomal abnormalities have distinct cumulative clinical pregnancy and cumulative live birth rates among patients undergoing assisted reproductive technology (ART). Methods Design: A retrospective cohort study. Setting: Department of Reproduction and Infertility in Chengdu Women’s and Children’s Central Hospital. Patients A total of 112 couples were in the exposed group with chromosomal abnormalities, and 226 couples without chromosomal abnormalities were in the control group, totalling 338 cases enrolled from 1 January 2017 to 31 December 2020. The control group (infertile couples without chromosomal abnormalities) was 1:2 matched by female age, type of infertility (primary, secondary), and type of ART (IVF, ICSI, or IUI). The primary outcomes were cumulative clinical pregnancy rate and cumulative live birth rate. Results The results indicated that chromosome abnormalities did not lead to significant differences in primary outcomes. The overall cumulative clinical pregnancy rate and cumulative live birth rate were not statistically different between the two groups (74.8% vs. 81.6%, p = .150) and (65.4% vs. 69.1%, p = .508). Further analysis revealed that there was also no significant difference in cumulative miscarriage rate between the two groups (13.9% vs. 20.3%, p = .213). Conclusions There were no significant differences in the cumulative clinical pregnancy rate or cumulative live birth rate between infertile couples with or without chromosomal abnormalities. KEY MESSAGES The prevalence of infertility is rising year by year worldwide. Carriers of chromosomal abnormalities undergoing ART have the similar cumulative clinical pregnancy rate or cumulative live birth rate. The data we analysed have a certain significance for clinical decision-making involving ART for couples with chromosomal abnormalities, and it provides a meaningful reference for patients and physicians in the selection of PGT.

According to the latest ART report for Europe, about 13% of pregnancies after frozen embryo transfer are multiple. Our objective was to analyse the impact on the multiple pregnancy rate of two eSFET (elective single frozen embryo transfers) versus a DFET (double frozen embryo transfer) in women aged under 38 years, who had not achieved pregnancy in their fresh transfer and who had at least two vitrified embryos of A/B quality. This study was conducted from January 2010 to June 2013 at a public hospital. The couples were divided into three groups. Group DFET: the first cryotransfer of two embryos (105 women); cSFET group: the only cryotransfer of a single vitrified embryo (60 women); eSFET group, individually vitrified embryos: 20 patients included in a clinical trial of single-embryo fresh and frozen transfer and 21 patients who chose to receive eSFET. The clinical pregnancy rate was 38.1% in the DET group and the cumulative clinical pregnancy rate was 43.3% in the eSFET group. There were no significant differences between the DFET and eSFET groups (30.0 vs 34.1%) in cumulative live birth delivery rate. The rate of multiple pregnancies varied significantly between the DFET and eSFET groups (32.5 vs 0%, p < 0.05). For good-prognosis women aged under 38 years, taking embryo quality as a criterion for inclusion, an eSFET policy can be applied, achieving acceptable cumulative clinical pregnancy and live birth rates and reducing multiple pregnancy rates.

Overweight and obese are important factors leading to the occurrence of long-term complications in women with polycystic ovary syndrome (PCOS). There has been controversy over whether dissatisfaction with pregnancy outcomes in PCOS patients is influenced by chronic inflammatory status or obesity. This retrospective study analyzed the levels of inflammatory factors in PCOS patients with different body mass index (BMI) groups and effective predictors of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancy outcomes. There were 273 women with PCOS diagnosed who completed serum inflammatory factors test between January 2017 and June 2022 were selected. The data of 7,649 infertility PCOS patients who received their first IVF/ICSI treatment in the Reproductive Center of Peking University Third Hospital during the period of the study were collected. Finally, 92 PCOS patients were included in the high BMI group, while 97 patients were included in the normal BMI group. Baseline characteristics were collected and the pregnancy outcomes were compared among the two groups. Then, serum inflammatory factors' effect on IVF/ICSI pregnancy outcomes were analyzed with age, anti-Mullerian Hormone (AMH) and BMI adjusted. PCOS patients in the high BMI group significantly had a lower number of oocytes retrieved and good quality embryos. The high BMI group PCOS patients had higher levels of IL-6 and lower cumulative clinical pregnancy and live birth rates. The level of GM-CSF was higher in the first cycle transfer and cumulative miscarriage group. High TNF-α was negatively correlated with the first transfer cycle and cumulative clinical pregnancy rates after age, AMH and high BMI adjusted. In addition, the cumulative live birth rate was negatively correlated with high IL-6, but the first cycle transfer and cumulative live birth rates were positively correlated with high IL-1β. For PCOS patients, in addition to BMI, attention should also be paid to inflammatory indicators. High levels of TNF-α and IL-6 were negatively correlated with pregnancy outcomes, but high IL-1β was positively correlated with live birth rates among PCOS patients. The level of GM-CSF was higher in miscarriage PCOS patients.

Day 2 embryo transfer (ET) and day 3 ET afford similar reproductive outcomes in the poor responder

Does surgery for colorectal endometriosis prior to IVF±ICSI have an impact on cumulative live birth rates?

Study question Are cumulative pregnancy rates different if supernumerary embryos are vitrified on day 5 instead of day 3? Summary answer Results do not show a significant difference in cumulative pregnancy rates between the vitrification day 3 and day 5 group. What is known already The pregnancy and live birth rates following IVF or ICSI treatment are higher after extended embryo culture and blastocyst transfer (day 5) compared to cleavage-stage (day 3) embryo transfer (Glujovski et al 2016). Cumulative pregnancy rates after fresh and frozen embryo transfers show no significant difference after one oocyte retrieval (OR) but only one study used vitrification for the cryopreservation of supernumerary embryos while four studies used a slow freezing protocol (Fernandez-Shaw et al., 2014). A retrospective analysis by De Vos et al., 2016 concluded significantly less embryo transfers were necessary until live birth for blastocyst-stage embryos. Study design, size, duration A Randomized Controlled Trial was performed in an academic center between 01/01/2018 and 31/07/2020. Patients were randomized in the vitrification day 3 or day 5 group. Primary outcome is the number of embryo transfers needed to reach ongoing pregnancy. Power calculation revealed that 75 patients were needed in each group, assuming a median of 4 transfers in the day 3 group versus a median of 2 transfers in the day 5 group to achieve pregnancy. Participants/materials, setting, methods Patients &amp;lt;38 years undergoing their first/second OR were randomized at the start of the cycle. Embryos with ≥6 cells, &amp;lt;25% fragmentation and equal blastomeres and blastocysts with expansion grade ≥2 with inner cell mass and trophectoderm score A/B were vitrified. A time-to-event analysis was performed with ongoing pregnancy as the event of interest and the number of embryo transfers as the time component. The statistical comparison was performed by a Cox proportional hazards model. Main results and the role of chance By December 2021, 234 transfers (96 fresh and 138 frozen) of 78 patients were performed in the vitrification day 3 group and 207 transfers (83 fresh and 113 frozen) of 80 patients in the vitrification day 5 group. The time-to-event analysis did not show a difference between both arms with regards to ongoing pregnancy as the primary study outcome (HR 1.25, 95% CI 0.81; 1.91, p = 0.31). The cumulative ongoing pregnancy rate after 8 transfers was 56% in the day 3 group versus 57% in the day 5 group. Median number of transfers till pregnancy was 6 versus 4, respectively. Similar results were found for the secondary study outcome (clinical pregnancy with fetal heart rate, HR 1.19, 95% CI 0.80; 1.80, p = 0.407). A total of 225 transfers (93 fresh and 132 frozen) of 78 patients were performed in the vitrification day 3 group and 201 transfers (92 fresh and 109 frozen) in the vitrification day 5 group. The cumulative clinical pregnancy rate after 8 transfers was 62% in the day 3 group versus 59% in the day 5 group. Median number of transfers till pregnancy was 6 versus 4, respectively. Limitations, reasons for caution Although power calculation revealed 75 patients are needed in each study group (β = 0.87, α &amp;lt; 0.05), numbers remain low. Wider implications of the findings A recent systematic review and cumulative meta-analysis of Marconi et al. (2021) suggests day 5 embryo transfer is associated with higher risk of preterm birth although evidence was low. Health/economic analyses should be taken into account to determine the most cost-effective strategy for patient and hospital/society. Trial registration number NCT04196036

Recombinant FSH increases live birth rates as compared to clomiphene citrate in intrauterine insemination cycles in couples with subfertility: a prospective randomized study

Clinical outcome of IVF-ET with conventional COS is unaltered by the presence of serum ANA when low-dose, short-term corticosteroid regimen is administered