Cumulative Live Birth Rate Research Articles

Dual trigger versus human chorionic gonadotropin trigger for blastocyst quality and cumulative live birth.

To evaluate the difference in the number of euploid blastocysts and cumulative live birth rate (LBR) between dual and human chorionic gonadotropin (hCG) triggers in poor and normal ovarian responders undergoing preimplantation genetic testing (PGT) cycles. This retrospective cohort study was enrolled from July 2018 to December 2021 and followed up until June 2024 at a single reproductive medical center. Overall, 1040 in vitro fertilization (IVF)-PGT and 784 frozen-thawed embryo transfer (FET) cycles were assessed. Dual (triptorelin acetate 0.2 mg and recombinant hCG [rhCG] 250 µg) or hCG (rhCG 250 µg) trigger was used for oocyte maturation in the gonadotropin-releasing hormone antagonist protocol and PGT cycles. We assessed the embryo outcomes and FET cumulative pregnancy outcomes. The number of oocytes retrieved (10.17 ± 5.22 vs 10.27 ± 5.14, P = 0.789), MII oocytes (8.24 ± 4.26 vs 8.28 ± 4.05, P = 0.888), blastocysts (2.16 ± 1.50 vs 2.12 ± 1.49, P = 0.729), euploid blastocysts (1.06 ± 1.14 vs 1.09 ± 1.23, P = 0.726), and the rate of cumulative LBR (24.9% vs 24.9%, P = 1.000) in the dual trigger group were comparable with those in the hCG group. The trigger method was not correlated with higher LBR based on logistic regression analysis (odds ratio[OR] = 1.040 [0.778-1.392], P = 0.790). For poor and normal ovarian responders, the dual trigger, compared with the hCG trigger, did not improve the PGT embryo outcomes and FET cumulative pregnancy outcomes.

Assessing the clinical value of day 7 blastocysts: a predictive model for preimplantation genetic testing for aneuploidy (PGT-A) cycles.

To identify the benefit of extending embryo culture until day (D)7 based on patients and cycle characteristics. A retrospective cohort study was conducted including 25,120 blastocysts from 5278 PGT-A autologous cycles between 2017 and 2022. A theoretical cumulative live birth rate (CLBR) was calculated by binomial density function. An increase of ≥ 5% in theoretical CLBR was considered a tangible benefit when obtaining ≥ 1 euploid D7 blastocyst and ≤ 3 euploid blastocysts from D5/D6. A predictive model was built considering the number of embryos eligible for extended culture until D7, number of blastocysts already biopsied on D5/D6, and patient's age. Euploidy rates decreased for blastocysts biopsied on D5, D6, and D7 (55.6%, 39.7%, and 27.1%, P < 0.001, respectively). The probability of tangible benefit was increased with more embryos available for extended culture until D7, was decreased with higher D5/D6 blastocysts already biopsied and for older patients. The overall AUC of the final model in the validation sets was 0.75 (95% CI 0.72-0.78). Based on the predictive model, in poor cycles (< 1% tangible benefit), the benefit rate from extended culture was 0.3% and for moderate, good, and best cycles (1-10%, 10-20%, and ≥ 20% tangible benefit) were 4.4%, 14.0%, and 29.3%, respectively. An application of the predictive model is available online for external testing: https://artfertilityclinics.shinyapps.io/WET-D7/ . The predictive model provides a decision-making tool to objectively identify cycles that would benefit from extending embryo culture until D7.

Intracytoplasmic sperm injection compared with in vitro fertilisation in patients with non-male factor infertility with low oocyte retrieval: a single-centre, retrospective cohort study

ObjectiveTo investigate the effects of in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) on the clinical outcomes of non-male factor patients aged >35 with three or fewer oocytes retrieved.DesignRetrospective...

Beyond the egg: sperm source does not impact cumulative live birth rates in autologous oocyte cryopreservation patients when adjusted for oocyte age.

To assess the impact of sperm source on cumulative live birth rate (CLBR) after oocyte thaw in autologous oocyte cryopreservation (AOC) patients. A retrospective cohort study of autologous oocyte thaw patients at an urban academic fertility center from 2006 to 2021. Patients were stratified by sperm source [partner sperm (PS) vs. donor sperm (DS)]. The primary outcome was CLBR per patient. Secondary outcomes were the oocyte survival rate and usable embryo rate. Statistics included Mann-Whitney U, Kruskal-Wallis, Fisher's exact, chi-square, two-sample t-tests, and multiple logistic regression (p < 0.05). A total of 653 patients were included; 455 (69.7%) used PS and 198 (30.3%) used DS. Time from the first AOC to the first thaw did not differ among DS and PS users (56.8 vs. 54.0months, p = 0.20). PS users were younger at AOC (37.9 vs. 38.5years, p < 0.001) and thaw (42.3 vs. 43.1years, p < 0.001). There were equivalent overall CLBRs (39.9% PS vs. 40.6% DS, p = 0.85) and CLBRs in patients < 35years at AOC (51.2% PS vs. 100% DS, p = 0.18), 35-37years at AOC (45.9% PS vs. 60.4% DS, p = 0.10), 38-40years at AOC (35.4% PS vs. 35.2% DS, p = 0.93), 41-42years at AOC (28.9% PS vs 14.3% DS, p = 0.21), and > 43years at AOC (12.5% PS vs 16.7% DS, p = 0.83) among PS and DS users. There were no significant differences in the oocyte survival (79% PS vs 80.5% DS, p = 0.08) or the proportion of patients with usable embryos (27.3% vs 27.8%, p = 0.70) between PS and DS groups. In AOC patients, CLBR, oocyte survival rate, and usable embryo rate did not differ based on sperm source.

Effect of Paternal Body Mass Index on Cumulative Live Birth Rates: Retrospective Analysis of 3048 Embryo Transfers in Couples Using Autologous Gametes

Obesity is a multifactorial disease present worldwide and correlated with hormonal alterations that may cause a decrease in reproductive outcomes and seminal quality. However, the specific mechanisms involved are unknown. This led us to examine the relationship between paternal body mass index (BMI) and clinical reproductive outcomes by evaluating the cumulative live birth rates (CLBRs) per number of embryo transfers (ETs), embryos replaced (EmbRs), and oocytes used (OUs) in consecutive treatments until achieving the first newborn. A retrospective study was performed, and Kaplan–Meier survival curves were created to observe CLBRs with regard to the paternal BMI, adjusted by relevant confounders through Cox regression models. The participants were couples undergoing intracytoplasmic sperm injection (ICSI) and ET in Spanish IVIRMA clinics using autologous gametes. The cohort was subdivided based on paternal BMI: normal (18.5–24.99 kg/m2) (N), overweight (25–29.99 kg/m2) (OV), or obese (≥30 kg/m2) (OB) patients. A total of 4750 ICSI cycles were included, encompassing 49,485 mature oocytes, 23,963 blastocysts, and 3048 ETs. When calculating CLBRs based on the number of ETs carried out until live birth was achieved, no statistically significant differences were found (p = 0.72). After adjusting for maternal age and BMI, female infertility diagnosis, the use of preimplantation genetic testing, and the number of ETs, Cox regression showed that there were no statistically significant differences between the BMI groups (HR: 0.94 [95% CI: 0.7–1.2]; p = 0.59). When calculating CLBRs considering EmbRs, there was a similarity between the BMI groups (p = 0.57). However, there were no statistically significant differences in the adjusted Cox regression (HR: 0.93 [95% CI: 0.7–1.2]; p = 0.51). Finally, when calculating CLBRs considering OUs, the results were comparable among BMI subgroups (p = 0.75), and there were no statistically significant differences with adjusted Cox regression (HR: 0.95 [95% CI: 0.8–1.2]; p = 0.66). In conclusion, paternal BMI was not associated with clinical reproductive outcomes when considering the ETs, EmbRs, or OUs needed to reach the first liveborn (LB).

One fresh cleavage-stage single embryo transfer (SET) plus one frozen-thawed blastocyst-stage SET or one fresh cleavage-stage double embryo transfer? A retrospective matched cohort study.

Are there significant differences in fertility outcomes between transferring two cleavage-stage embryos in a single fresh cycle and transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle? In women aged <38 years with two embryos available, transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle increased live birth rates and decreased multiple live birth rates compared to transferring two cleavage-stage embryos in a single fresh cycle. The strategy of repeated single embryo transfer (SET) has emerged as a solution to address the reduced live birth rates associated with SET per cycle. There is substantial evidence indicating that the cumulative live birth rate after repeated SET is comparable to that of double embryo transfer (DET), while significantly reducing the incidence of multiple pregnancies. Evidence regarding the outcomes of transferring two cleavage-stage embryos in a single fresh cycle versus transferring one cleavage-stage embryo in one fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle is scarce. This study is a retrospective matched cohort study, where data were gathered from the clinical database of women who underwent IVF treatment at the Reproductive Center of Peking University Third Hospital between January 2011 and December 2019, with follow-up extending until December 2021. The study group included cycles with a fresh cleavage-stage SET and a subsequent frozen-thawed blastocyst-stage SET (2xSET, N = 976). Fresh cleavage-stage DET was the control group (DET, N = 976). Included cycles were divided into subgroups based on age (≥38 years vs <38 years) and total number of utilizable (transferred or cryopreserved) embryos (=2 vs >2). The duration of infertility, prevalence of unexplained infertility, and controlled ovarian stimulation regimes differed significantly between the two groups and were adjusted for in the further analysis. We observed a significant increase in clinical pregnancies (55.5% vs 42%, adjusted odds ratio (OR) 1.87 [1.55-2.26]) and live births (44.8% vs 34.5%, adjusted OR 1.63 [1.35-1.97]) in favor of the 2xSET group. The preterm birth rate was lower in the study group (adjusted OR 0.64 [0.42-0.96]). Neonatal birth weight of singletons was similar between the two groups (adjusted B 4.94 g [-84.5 to 94.4]). The beneficial effect on the live birth rate disappeared in cases where aged 38 years and older or when only two embryos were utilizable. This study is limited by differences in baseline characteristics of the two groups. Analyzing two consecutive SETs at the cleavage stage was not feasible. Additionally, the homogeneous population limits generalizability to other ethnic groups, which should be considered when interpreting the results broadly. We recommend a combination strategy for women under 38 years old and with more than two embryos available: transfer one cleavage-stage embryo in the fresh cycle, followed by one blastocyst-stage embryo in the subsequent frozen-thawed cycle. This strategy reduces the risk of blastocyst culture failure while maintaining a high success rate. It offers hope to families seeking additional children and avoids unnecessary embryo disposal. B.W.M. had received grants from NHMRC, Ferring, Merck, and Guerbet, consulting fees and stock options from ObsEva, is on the advisory board of ObsEva, and reports consultancy for Guerbet, none of which are in relation to the present manuscript. All other authors have no conflict of interest to declare. N/A.

Recipients' age, fresh embryo and blastocyst-stage embryo transfer as favorable factors in a transnational oocyte donation program.

In Italy, egg donation is being allowed again following the ruling by the Constitutional Court N. 162/2014. Nevertheless, the number of voluntary donors is insignificant, probably because no reimbursement is provided. Therefore, the great majority of egg donation cycles are performed by using imported cryopreserved oocytes from foreign countries. However, recent evidence has questioned the overall efficacy of this strategy in comparison with the shipment of frozen sperm and vitrified embryos. Retrospective cohort study, conducted at ANDROS Day Surgery Clinic Palermo, Italy in the period 2016-2022, with the objective of evaluating the efficiency of each batch of vitrified oocytes, in terms of completed cycles. The cryopreserved donated oocytes came from a single Spanish clinic (Next Fertility, Valencia, Spain). The primary outcome was the cumulative live birth rate (CLBR). The secondary outcomes were the cumulative ongoing pregnancy rate (COPR), the cumulative clinical pregnancy rate (CCPR) and the miscarriage rate. The CLBR totaled 35.1%, the COPR 36.8%, the CCPR 49.2% and the miscarriage rate 24.7%. In the multivariate analysis, the probability of success was significantly higher in younger recipients, in fresh embryo transfer and in blastocyst-stage embryo transfer. Our "transnational" donation program with vitrified oocytes has good success rates. The main focus of our analysis is the negative effect of advancing recipient age on success rates, outlining a possible, important role of age-related uterine factor on implantation mechanisms. This aspect should be emphasized during the counselling with couples much more than is routinely done.

Outcomes of female fertility preservation with cryopreservation of oocytes or embryos in the Netherlands: a population-based study.

What are the reproductive outcomes of patients who cryopreserved oocytes or embryos in the context of fertility preservation in the Netherlands? This study shows that after a 10-year follow-up period, the utilization rate to attempt pregnancy using cryopreserved oocytes or embryos was 25.5% and the cumulative live birth rate after embryo transfer was 34.6% per patient. Fertility preservation by freezing oocytes or embryos is an established treatment for women with a risk of premature ovarian failure (caused by a benign or oncological disease) or physiological age-related fertility decline. Little is known about the success of cryopreservation, the utilization rate of oocytes or embryos, or the live birth rates. A retrospective observational study was performed in the Netherlands. Data were collected between 2017 and 2019 from 1112 women who cryopreserved oocytes or embryos more than 2 years ago in the context of fertility preservation in 10 IVF centers in the Netherlands. A total of 1112 women were included in this study. Medical files and patient databases were used to extract data. Women were categorized based on indication of fertility preservation: oncological, benign, or non-medical. To indicate statistical differences the t-test or Mann-Whitney U test was used. Kaplan-Meier analyses were used for time endpoints, and log-rank analyses were used to assess statistical differences. The study protocol was approved by the medical ethics committee. Fertility preservation cycles have been performed increasingly over the years in the Netherlands. In the first years, less than 10 cycles per year were performed, increasing to more than 300 cycles per year 10 years later. Initially, embryos were frozen in the context of fertility preservation. In later years, cryopreservation of oocytes became the standard approach. Cryopreservation of oocytes versus embryos resulted in comparable numbers of used embryos (median of 2) for transfer and comparable live birth rates (33.9% and 34.6%, respectively). The 5-year utilization rate was 12.3% and the 10-year utilization rate was 25.5%. The cumulative clinical pregnancy rate was 35.6% and the cumulative live birth rate was 34.6% per patient. Those who had fertility preservation due to benign diseases returned earlier to use their cryopreserved embryos or oocytes. The follow-up period after the fertility preservation procedure varied between patients in this study and not all frozen oocytes or embryos had been used at the end of this study. This might have led to underestimated outcomes reported in this study. Furthermore, intention to treat cannot be fully determined since women who started the fertility preservation procedure without success (cancellation due to low response) were not included in this study. This study provides data on the reproductive outcomes after various indications of fertility preservation. This knowledge can be informative for professionals and future patients to improve counseling and informed decision making regarding ovarian stimulation in the context of fertility preservation. No funding was obtained for this study. The authors have no conflicts of interest to declare related to this study. V.T.H. received grants paid to the institute for studies outside the present work from AstraZeneca, Gilead, Novartis, Eli Lily, Pfizer, and Daiichi Sankyo. V.T.H. received consulting fees from Eli Lily outside the present work. M.G. received grants paid to the institute for studies outside the present work from Guerbet and Ferring. E.M.E.B. received a grant from The Dutch Network of Fertility Preservation for a study outside the present work. N/A.

Identify high-risk DOR women ≤ 35 years old following assisted reproduction technology through cutoffs of anti-mullerian hormone and antral follicle counts

BackgroundFemales with diminished ovarian reserve (DOR) have significantly lower cumulative live birth rates (CLBRs) than females with normal ovarian reserve. A subset of young infertile patients, whose ovarian reserve is declining but has not yet met the POSEIDON criteria for DOR, has not received the attention it merited. These individuals have not been identified in a timely manner prior to the initiation of assisted reproductive technology (ART), leading to suboptimal clinical pregnancy outcomes. We categorized this overlooked cohort as the “high-risk DOR” group.ObjectiveThe primary aim of this study was to identify high-risk DOR patients through anti-Mullerian hormone (AMH) and antral follicle counts (AFCs).MethodsA total of 10037 young women (≤ 35 years old) who underwent their first initial oocyte aspiration cycle at a single reproductive medicine center were included and further classified into three groups, based on the thresholds for AMH and AFC established through receiver operating characteristic (ROC) analysis and in alignment with the POSEIDON criteria. Two ROC analyses were performed to identify the cutoff values of AMH and AFC to obtain one viable embryo (one top-quality embryo or one viable blastocyst). The cutoffs of ROC were measured by sensitivity and specificity. The primary outcome was the cumulative live birth rate (CLBR) per oocyte aspiration cycle. The secondary outcomes included the number of oocytes retrieved and the number of viable embryos formed. Pearson’s chi-square tests were conducted to compare the clinical outcomes among the three groups. Furthermore, univariate logistic regression analyses were performed to investigate the associations between ovarian reserve and clinical outcomes. All of the above comparisons between the high-risk DOR and NOR were further confirmed by propensity score matching (PSM) (1:1 nearest-neighbor matching, with a caliper width of 0.02).ResultsAccording to the ROC analyses and POSEIDON criteria, the present study identified a population of high-risk DOR patients (1.20 ng/mL < AMH values < 2.50 ng/mL, with 6 ≤ AFC ≤ 10; n = 682), and their outcomes were further compared to those of DOR patients (positive control, AMH values ≤ 1.2 ng/mL, and/or AFC ≤ 5; n = 1153) and of NOR patients (negative control, 2.5 ng/mL ≤ AMH values ≤ 5.5 ng/mL, and 11 ≤ AFC ≤ 20; n = 2649). Patients in the high-risk DOR group had significantly lower CLBRs than those in the NOR group (p < 0.001) but higher CLBRs than those in the DOR group (p < 0.001). Logistic regression further demonstrated that high-risk DOR was associated with a lower likelihood of cumulative live birth chance (OR 0.401, 95% CI: 0.332–0.486, p < 0.001) than NOR was, with a greater likelihood of cumulative live birth chance (OR 1.911, 95% CI:1.558–2.344, p < 0.001) than DOR was. To investigate the effects of embryo development stage, the outcomes of D3 embryos and blastocysts were analyzed separately. Significant differences in pregnancy outcomes were detected only in D3 embryo ET cycles among the three groups (high-risk DOR vs. NOR, all p < 0.05; DOR vs. NOR, all p < 0.05). DOR/high-risk DOR did not influence the pregnancy loss rates or pregnancy outcomes (clinical pregnancy rates and ongoing pregnancy rates) per positive HCG cycle (all p > 0.05). After PSM, the differences in ovarian response and pregnancy outcomes between the high-risk DOR and NOR groups were consistent with the results before PSM.Conclusion(s)Our study revealed that the CLBR of the high-risk DOR patients was significantly lower than that of females with normal ovarian reserve and greater than that of females with DOR. The values of AMH ranging from 1.2 to 2.5 and AFC ranging from 6 to 10 appeared to constitute meaningful thresholds in females with mildly reduced ovarian reserve.

Two-year cumulative live-birth rates and maximum number of transfer cycles in women aged ≥ 40 years

This retrospective study aimed to clarify the cumulative live-birth rates (CLBRs) and cost per live-birth (LB) to evaluate the validity of frozen–thawed embryo transfer without preimplantation genetic testing for aneuploidy (PGT-A) in women aged ≥ 40 years. The study included 1,011 patients aged ≥ 40 years who underwent their first oocyte retrieval at our hospital between January 2010 and September 2017. They were followed up for up to two years or until either treatment discontinuation or a pregnancy that resulted in a live birth. The 2-year CLBRs were 55.6%, 39.0%, 31.3%, 19.1%, 10.6%, 4.4%, and 0% for patients aged 40, 41, 42, 43, 44, 45, and > 46 years, respectively. In approximately 80% of LB cases, patients aged 40–42 years and 43–44 years became pregnant by the fourth and second transfers, respectively. Costs per LB were $30,207, $49,034, $66,345, $102,759, and $195,862 for patients aged 40, 41, 42, 43, and 44, respectively. Cost per LB for each number of transfers reached $300,000 and $ 450,000 for the third transfer at 42 and 43 years of age, respectively. For cost-effectiveness, up to two ET cycles are recommended for patients aged 42–43, and none for patients aged ≥ 44 years.

Women may not benefit from repeated frozen embryo transfers: a retrospective analysis of the cumulative live birth rate of 43972 women.

Which specific groups of women would not benefit from repeated frozen embryo transfers (FETs)? Women over 45 years of age should stop treatment after three FET attempts due to the absence of further benefits, while women aged 40-45 years and those with a diminished ovarian reserve and other causes of infertility have a lower chance of improving their cumulative live birth rate (CLBR) within five FET cycles and experience fewer advantages from repeated transfers. In real-life scenarios of ART, women who fail to achieve a live birth often choose to undergo repeated FETs via the freeze-all strategy. This retrospective study included 43972 women who underwent 86496 oocyte retrieval cycles and 82022 FET cycles between January 2010 and March 2023 under the freeze-all strategy. We categorized the population based on the female's age at the first oocyte pick-up (OPU) cycle (Groups 1-6: <30, 30-34, 35-39, 40-42, 43-44, and ≥45 years of age), number of retrieved oocytes at the first OPU cycle (Groups 1-5: 1-5, 6-10, 11-15, 16-20, and >20 oocytes), and causes of infertility (Groups 1-9: tubal factor, male factor, polycystic ovary syndrome, diminished ovarian reserve, endometriosis, other uterine factors, combined factors, unexplained infertility, and other infertility) to analyse their CLBRs within different FET cycles via Kaplan-Meier analysis (optimistic method) and the competing risk method (conservative method). We utilized multivariate Cox and Fine-Gray models to examine the associations between the CLBR and age, the number of retrieved oocytes, and nine causes of infertility. The CLBR decreased with increasing female age over five FET cycles (Groups 1-6: optimistic method: 96.4%, 94.2%, 86.0%, 50.2%, 23.1%, and 10.1%; conservative method: 87.1%, 82.0%, 67.8%, 33.9%, 13.8%, and 3.5%, respectively). Moreover, there was an increasing trend in the number of retrieved oocytes (Groups 1-5: optimistic method: 82.5%, 91.7%, 93.6%, 94.1%, and 96.2%; conservative method: 58.6%, 76.7%, 84.8%, 88.0%, and 92.5%, respectively). Furthermore, the CLBR varied across different causes of infertility (Groups 1-9: optimistic method: 91.7%, 93.1%, 96.6%, 79.2%, 89.9%, 76.1%, 90.0%, 92.9%, and 35.4%; conservative method: 77.3%, 79.4%, 88.9%, 46.7%, 72.7%, 62.1%, 74.4%, 78.8%, and 20.1%, respectively). Calculating the actual CLBR for each person is difficult because some patients have remaining embryos that have not been transferred; additionally, the current statistical methodology uses both optimistic and conservative methods to calculate the CLBR, and in real life, the CLBR falls between the optimistic and conservative curves. Our study is the first to identify specific subgroups of women who fail to benefit from repeated FETs and who require rational discontinuation of treatment following unsuccessful transfer. This study was financially supported by grants from the National Natural Science Foundation of China (grant numbers: 82271732 to Y.K., 82071603 to L.W., 82001502 to Y.L., and 82201888 to X.S.). The authors declare that they have no conflicts of interest in the present study. N/A.

Improved reproductive outcomes in normogonadotropic oligomenorrheic women undergoing ovarian stimulation with intrauterine insemination: a retrospective cohort analysis of real-world data.

This study aimed to evaluate the comparative reproductive outcomes of ovarian stimulation combined with intrauterine insemination using partner's sperm (OS-IUI) in eumenorrheic and normogonadotropic oligomenorrheic women. A retrospective cohort study was conducted, including 3833 couples who underwent 5920 cycles of OS-IUI between June 2013 and March 2019. Participants were stratified into two cohorts based on menstrual regularity: eumenorrheic and normogonadotropic oligomenorrheic. The primary outcome measured was the live birth rate (LBR) per cycle and cumulative LBR per couple. Secondary outcomes encompassed the clinical pregnancy rate (CPR) per cycle, miscarriage rate, and multiple pregnancy rate. Propensity score matching (PSM) was utilized to balance maternal baseline characteristics. Prior to PSM, significant differences in CPR, LBR and cumulative LBR were observed between eumenorrheic and oligomenorrheic women, favoring the latter (CPR: 11.16% vs. 18.75%; LBR: 9.02% vs. 14.96%; cumulative LBR: 13.60% vs. 24.25%, P < 0.001). These differences persisted post-PSM (CPR: 9.74% vs. 19.29%; LBR: 7.30% vs. 16.29%; cumulative LBR 7.76% vs. 19.90%, P<0.001). Multivariate regression analyses revealed that menstrual status was a significant independent predictor of both CPR (adjusted odds ratio [OR]=1.83 before PSM, 2.24 after PSM) and LBR (adjusted OR=1.90 before PSM, 2.46 after PSM). In the subgroup analysis, female age was identified as the sole predictor of reproductive outcomes in oligomenorrheic women undergoing OS-IUI. Conversely, in eumenorrheic women, factors such as age, duration of infertility, body mass index (BMI), ovarian stimulation agents, and the number of dominant follicles were significant influencers of CPR and LBR. Normogonadotropic oligomenorrheic women demonstrated improved reproductive outcomes with OS-IUI, suggesting that tailored treatment strategies based on menstrual regularity could optimize success rates in infertility management.

Correlation of adenomyosis features to live birth rates after the first IVF/ICSI treatment, when using the revised Morphological Uterus Sonographic Assessment group definitions.

Data regarding the impact of adenomyosis on the outcomes after invitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment are conflicting. Standardized diagnostic criteria are prerequisites for studying a potential association between adenomyosis and IVF/ICSI treatment outcomes. This study aims to examine the cumulative live birth rate (CLBR) after the first IVF/ICSI treatment in women with or without direct or indirect features of adenomyosis, using the revised Morphological Uterus Sonographic Assessment (MUSA) group definitions. This was a prospective cohort study of 1037 women aged 25-≤39 years, undergoing their first IVF/ICSI treatment between January 2019 and October 2022. The presence of MUSA features of adenomyosis was assessed prior to treatment start. The CLBR after the first IVF/ICSI treatment was 424/1037 (40.9%, 95% CI, 37.9-43.8) in the total cohort. Women with direct features of adenomyosis had lower CLBR, 25/102 (24.5%; 95% CI, 17.5-31.5) than women without, 399/935 (42.7%; 95% CI, 39.5-45.8), p < 0.001. The adjusted relative risk (aRR) for live birth for women with direct features of adenomyosis compared to women without was 0.62 (95% CI, 0.43-0.88), p = 0.007. Direct features were associated with a higher risk of miscarriage after frozen embryo transfer, aRR 2.88 (95% CI, 1.49-5.57), p = 0.002. Women with indirect features had a lower CLBR [50/188 (26.6%, 95% CI, 20.3-32.9)] than women without [399/935, (42.7%, 95% CI, 39.5-45.8)], aRR 0.58 (95% CI, 0.45-0.75), p < 0.001. For features located in the inner myometrium, the aRR for live birth was 0.29 (95% CI 0.11-0.74), p = 0.010 and for the outer myometrium 2.61 (95% CI 1.42-4.8), p = 0.002. An interrupted junctional zone was the single feature that impacted CLBR the most. The presence of direct or indirect MUSA features of adenomyosis correlates to reduced live birth rates in women undergoing their first IVF/ICSI treatment. Features located in the inner myometrium, particularly an interrupted junctional zone, reduced the chance of live birth the most, whereas location in the outer myometrium was associated with higher chances of live birth. Systematic ultrasound examinations should be considered for women scheduled for IVF/ICSI treatment, for adequate counseling on the chances of successful treatment.

In-vitro fertilization experience with follitropin-delta in poor responders identified by POSEIDON Classification.

Controlled ovarian stimulation during in-vitro fertilization (IVF) is personalized based on anticipated hyper, normal, poor response. With respect to poor responders, who are often treated using higher gonadotropin dosing and combination of urinary and recombinant gonadotropins (rFSH) with marginal benefit, we report our experience with a newer, more potent rFSH (Follitropin-δ) undergoing IVF. Retrospective analysis of all IVF cycles in which follitropin-δ was used alone or combined with urinary gonadotropins over a 3-year period. Patients were grouped according to the POSEIDON Classification as expected low responders (POSEIDON 3-4; AMH<1.2; N.=45), unexpected low responders (POSEIDON 1-2; retrieval of ≤9 oocytes; N.=67) and those with a normal response (N.=93). Demographic, stimulation (including target number of retrieved oocytes [8 to14]), embryology and clinical outcome parameters (clinical pregnancy rate [CPR], live birth rate [LBR], cumulative live birth rate [cLBR]) were compared. Those categorized as POSEIDON patients were older, had lower ovarian reserve, were more likely to use a mixed protocol, less likely to reach the target oocytes retrieved (35.7% vs. 51.6%, P<0.001), and had a lower cLBR per patient (29.5% vs. 38.7%, P=0.006) when compared to non-POSEIDON patients. Expected low responders (POSEIDON 3-4) were older and had lower AMH when compared to unexpected low responders (POSEIDON 1-2), but no differences in the target of oocytes retrieved (33.3% vs. 37.3%, P=0.66) and cLBR (28.9% vs. 37.3%, P=0.06) were noted. In expected low responders, follitropin-δ can be used to optimize oocyte collection and clinical outcome though one may need to deviate from the algorithm-suggested dose. Future studies should explore stimulation modifications in unexpected low responders.

Progestin-primed ovarian stimulation

The use of progestins for the prevention of premature ovulation during ovarian stimulation is called progestin-primed ovarian stimulation (PPOS). Response to ovarian stimulation with PPOS and gonadotropin-releasing hormone (GnRH) analogs seem to be similar with the clinically insignificant differences being explained by endocrine characteristics as expected. PPOS has the advantage of oral administration and lower medication cost than GnRH analogs, but the mandatory cancellation of an otherwise possible fresh embryo transfer can render PPOS less cost-effective if a fresh transfer would have been possible. Oocytes collected in PPOS cycles have similar developmental potential, including blastocyst euploidy rates. Frozen embryo transfer outcomes of PPOS and GnRH analog cycles seem similar both in terms of ongoing pregnancy/live birth rates and obstetric and perinatal outcomes. While some studies reported lower cumulative live birth rates with PPOS, they suffer from methodological issues, including arbitrary definitions of cumulative live birth rates. PPOS has been used in all patient types with consistent results and seems a patient-friendly and cost-effective choice when a fresh embryo transfer is not intended.

Male and female human papilloma virus infection and assisted reproductive technology outcomes: A comprehensive assessment from prevalence in semen to obstetric outcomes.

Infertility, affecting approximately 16% of the global population, has led to increased reliance on reproductive medicine. The impact of human papillomavirus (HPV) infection in one or both partners on outcomes of Assisted Reproduction Technologies (ART) remains unclear. This prospective cohort study aimed to evaluate prevalence and effects of HPV infection in subjects and couples candidates to ART. A total of n = 510 men and n = 246 women were included and n = 145 couples (n = 290 individuals) had both partners enrolled in the study. The HPV semen infection rate was 17% (95% CI: 14-20) with HPV-42, HPV-16, HPV-53 and HPV-51 as the most frequently detected genotypes. In women, 26% (95% CI: 21-32) tested HPV-positive in cervical swabs. In 6% (95% CI: 3-11) of the couples, both partners were positive but only three couples shared the same genotypes (HPV-16; HPV-39, HPV-51, and HPV-42; HPV-31). Follicular fluids were positive in 20% (95% CI: 11-33) of samples, showing genotype discrepancies with cervical tests. Semen treatment could not completely eliminate the virus in positive samples but reduced the positivity to one-third. No significant differences in semen and embryological variables, clinical pregnancy and live birth rates, neonatal and obstetrics outcomes were observed in subjects with positivity in semen or cervix compared to respective negative groups. Cumulative live birth rates per oocyte retrieval in couples where both partners were negative or both were positive did not differ, being 37% (95% CI: 28%-47%) and 44% (95% CI: 19-73), respectively. In conclusion, HPV testing should not be considered a prerequisite for accessing ART treatments. Robust inferences for natural fertility cannot be made using our findings, as the ART setting does not fully reflect natural conditions.

Legal framework and IVF outcomes: a comparative analysis of fresh and frozen embryo transfers in Switzerland

Research question: To what extent do legislative measures impact standard reproductive outcome parameters? Design: Retrospective cohort study using data from the Swiss national IVF registry analysing the outcomes of 13908 women undergoing ETs resulting from their first lifetime oocyte retrieval before (2014-2016) or after (2020-2022) the revised legislation, allowing extended culture for 12 zygotes. Live birth rates (LBR) and cumulative LBR (cLBR) were compared in fresh and frozen ET strategies in both periods. Adjusted multivariable mixed model analyses were performed to determine odds ratios (OR) and incidence rate ratios (IRR). ResultsBefore the revised legislation, LBR was higher in fresh compared to frozen ET (27.2% vs. 22.7%). After the revised legislation, LBR was lower in fresh ET (29.3% vs. 36.3%) and cLBR was higher in freeze-all strategy (cLBR: 59.0% vs. 39.8%). However, in a multivariable analysis, fresh and frozen ETs did not differ in the odds of live birth (OR = 1.08, 95% CI: 0.95-1.22) and freeze-all were not found to be more effective than fresh strategies (IRR = 1.12, 95% CI 0.98 - 1.27). In a subgroup analysis, fresh blastocyst ET showed higher LBR than cleavage stage ET (OR = 2.01, 95% CI 1.62-2.49). ConclusionThe change in national legislation provided the unique opportunity to evaluate the legal impact on reproductive outcomes: Besides a reduction of multiple deliveries, LBR of frozen ET improved, resulting in a comparable success of fresh and frozen transfer strategies. In addition to technological improvement, the legal framework influences the evolution of clinical practice, thereby contributing to enhanced reproductive outcomes.

No impact of a positive Chlamydia trachomatis serology on live-birth rate after intra-uterine insemination

ObjectiveTo study the impact of a CT serology on intrauterine insemination (IUI) cumulative live-birth rate (cLBR) in women with documented bilateral tubal patency. DesignCohort study SubjectsInfertile women with documented bilateral tubal patency and medical indication of IUI matched on the following criteria: woman's age, number of cycles completed and number of motile sperm inseminated (NMSI). ExposureThis retrospective, observational and monocentric cohort study compared women with positive CT serology matched 1:1 to control women with negative CT serology. Main outcome measuresCumulative LBR, rates of clinical pregnancy, spontaneous abortion, biochemical pregnancy. ResultsA total of 71 women in the CT positive group were matched to 71 women in the negative CT group, leading to compare 136 cycles per group. No statistically significant difference was observed between groups regarding the demographic and medical characteristics of couples. Cumulative LBR per woman was similar in both groups with 32.4% (n = 23) in the negative serology group Vs 25.4% (n = 18) in the positive CT group (NS). The rates of clinical pregnancy, spontaneous abortion, biochemical pregnancy were comparable between the two groups. ConclusionIn a population of infertile women with patent tubes, our study suggests that the serological status for CT has no impact on the IIU cLBR.

Effect of Preimplantation Genetic Testing for Aneuploidies on Live Birth Outcomes and the Influencing Factors in Women of Advanced Maternal Age

To investigate effect of preimplantation genetic testing for aneuploidies (PGT-A) on the reproductive outcomes of women of advanced maternal age (AMA) (≥38 years), and to analyze factors influencing the live birth rate in AMA women who have received PGT-A. A retrospective cohort study was conducted. AMA women undergoing PGT-A were enrolled in the PGT-A group. All of them underwent their first oocyte retrieval cycle between January 2019 and June 2023. AMA women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and their first oocyte retrieval cycle over the same period of time were enrolled in the control group (the non-PGT-A group) via propensity score matching. The PGT-A group and the non-PGT-A group each included 193 cycles, which were followed up until January 2024. Follow-up concerning live births was completed for all oocyte retrieval cycles conducted between January 2019 and October 2022. The reproductive outcomes were compared between the two groups. The primary outcome indicator was cumulative live birth rate (CLBR) per oocyte retrieval, while the secondary outcome indicators were cumulative clinical pregnancy rate (CCPR) per oocyte retrieval and spontaneous abortion rate. For the 145 cycles in the PGT-A group with completed live birth follow-up, binary logistic regression analysis and receiver operator characteristic (ROC) curves were used to analyze the influencing factors of live birth rates. A total of 145 cycles in the PGT-A group and 161 cycles in the non-PGT-A group completed follow-up for live births. The CLBR per oocyte retrieval of the PGT-A group was 25.52% (37/145), while that of the non-PGT-A group was 28.50% (46/161), with no significant difference being observed between the two groups (P<0.05). Of the 193 oocyte retrieval cycles in each group, 53 cycles in the PGT-A group and 72 cycles in the non-PGT-A group resulted in clinical pregnancies, with the difference in the CCPR per oocyte retrieval being statistically significant (27.46% vs. 37.31%, P<0.05). Concerning clinical pregnancies, the spontaneous abortion rate of the PGT-A group was lower than that of the non-PGT-A group, with the difference being statistically significant (7.55% vs. 25.00%, P<0.05). In AMA women who had undergone PGT-A for reproductive assistance, maternal age (odds ratio [OR]=0.786, 95% confidence interval [CI]: 0.635-0.973) and the antral follicle count (AFC) (OR=1.110, 95% CI: 1.013-1.216) were correlated with the outcome of live births outcome. The probability of live births decreased with increasing maternal age and decreasing AFC. When the female age was ≥42 years or when AFC≤8, the expected live birth outcome of PGT-A assisted pregnancy was poor. PGT-A does not affect the CLBR per oocyte retrieval in AMA women, but it can effectively reduce the risks of implantation failure and spontaneous abortion due to fetal aneuploidies. For PGT-A-assisted pregnancy in AMA women, maternal age and AFC are important factors affecting the live birth outcomes.

The efficacy of orally administered L-carnitine in alleviating ovarian dysfunctions has laid the foundation for targeted in vivo use: a study employing self-control and propensity score matching.

This study aimed to evaluate the effectiveness of oral L-carnitine administration in patients after treatment failure to lay the groundwork for targeted in vivo use. A total of 515 In Vitro Fertilization (IVF) patients undergoing subsequent cycles were included after applying exclusion criteria. They were divided into a control group of 362 patients and a study group of 153 patients who received oral L-carnitine until oocyte retrieval.140 patients were matched according to maternal age, infertility duration, body mass index (BMI), day three top-quality embryos rate, by propensity score matching (PSM). The study investigated the relationship between L-carnitine treatment and in vivo oocyte maturation, normal fertilization, and subsequent embryo development. Following PSM, initial differences in BMI and Day3 top-quality embryo rate between groups were nullified, we created two comparable cohorts with highly similar characteristics. In the subsequent cycles, the study group showed significant improvements in in vivo oocyte maturation rate at retrieval (p=0.002), normal in vitro fertilization rate (p=0.003), blastocyst formation rate (p=0.003), and usable blastocyst rate compared to controls. Although there was no significant difference in the top-quality embryo rate on Day 3, the study group showed a 10% increase in the upper quartile (55.35% vs. 66.67%). The cumulative clinical pregnancy and live birth rates showed a significant improvement (59.82% vs. 68.42%,p=0.004, 47.41% vs. 59.80%, p=0.002). Furthermore, self-control analysis revealed substantial enhancements (p<0.001) in all outcome measures following L-carnitine administration, resulting in the birth of 74 healthy neonates without congenital anomalies. We theorized that daily oral intake of L-carnitine before oocyte retrieval could boost oocyte quality and embryonic development, thus improving IVF outcomes. Ongoing investigations hold the potential to offer valuable insights into the applications and mechanisms underlying the therapeutic effectiveness of L-carnitine.