Impact of dehydroepiandrosterone sulfate and free androgen index on pregnancy and neonatal outcomes in PCOS patients.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with infertility and pregnancy complications. The pathogenesis of PCOS and its impact on reproductive function may be influenced by the source of androgens, including testosterone, free androgen, dehydroepiandrosterone sulfate (DHEAS). However, the differential effects of these androgen on pregnancy and neonatal outcomes and the cut-off value of East Asian population with PCOS remain unclear. METHODS: A retrospective cohort study was conducted at the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University from January 2015 to November 2022, involving 636 cycles of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Subgroup analyses were performed using cut-off values of 6.4 for free androgen index (FAI), 9.5 µmol/L for DHEAS. Pregnancy and neonatal outcomes were compared between groups. Restricted cubic spline (RCS) was used to identify significant cut-off values affecting pregnancy. RESULTS: Higher FAI levels (> 6.4) were associated with decrease in clinical pregnancy rate (PR) (50.61% vs. 41.66%, p = 0.024), live birth rate (LBR) (42.42% vs. 32.35%, p = 0.011). When DHEAS levels exceeded 9.5 µmol/L, there was a significant decrease in clinical PR (51.27% vs. 42.73%, P = 0.039), LBR (42.73% vs. 32.73%, P = 0.012). Negative correlations were also observed between DHEAS levels and cumulative pregnancy rate (70.57% vs 56.62% p = 0.002) and cumulative live birth rate (CLBR) (59.35% vs 43.37%, p = 0.0007). Both FAI and DHEAS elevated is associated with the lowest clinical pregnancy rate (37.84%). Conversely, when solely FAI is elevated, the pregnancy rate increases to 52.38%, while an elevation in DHEAS alone is associated with a pregnancy rate of, both of which are lower than when neither FAI nor DHEAS are elevated (60.68%). The live birth rates exhibit a similar trend (30.00% vs 40.00% vs 41.83% vs 44.48%). RCS revealed a significant decrease in CPR and CLBR when DHEA levels exceeded 7.69 umol/L, while the cut-off value of FAI was 6.36 for CPR and CLBR. CONCLUSION: In conclusion, PCOS patients with biochemical hyperandrogenism show unsatisfactory clinical PR and CLBR when undergoing assisted reproductive technology (ART). This may be attributed to the influence of both adrenal-derived DHEAS and ovarian-derived FAI on the unfavorable pregnancy outcomes.

Age-related increase in live-birth rates of first frozen thaw embryo versus first fresh transfer in initial assisted reproductive technology cycles without PGT.

BACKGROUND: The landscape of assisted reproductive technology (ART) has seen a significant shift towards frozen-thawed embryo transfers (FET) over fresh transfers, driven by technological advancements and clinical considerations. This study aimed to compare live birth outcomes between primary FET and fresh transfers, focusing on cycles without preimplantation genetic testing (PGT), using United States national data from the SART CORS database spanning from 2014 to 2020. METHODS: We performed a retrospective cohort study of autologous first ART cycles without PGT comparing primary embryo transfer (frozen thaw vs. fresh) success rates from the 2014-2020 SARTCORS database. Live-birth rates (LBR) and cumulative live-birth rates (CLBR) were compared between first FET versus first fresh embryo transfer from an index retrieval. Multivariate logistic regression (MLR) determined association between live birth outcomes and method of transfer. In a subsequent sub-analysis, we compared these two embryo transfer methods among patients with either diminished ovarian reserve (DOR) or male factor infertility. RESULTS: 228,171 first ART cycles resulted in primary embryo transfer. 62,100 initial FETs and 166,071 fresh transfers were compared. Initial FETs demonstrated higher LBR and CLBR compared to fresh transfers (LBR 48.3% vs. 39.8%, p < 0.001; CLBR 74.0% vs. 60.0%, p < 0.0001). MLR indicated greater chances of live birth with FET across all age groups, with adjusted odds ratio (aOR) of live-birth incrementally increasing with advancing age groups. For DOR cycles, LBR and CLBR were significantly higher for FET compared to fresh (33.9% vs. 26.0%, p < 0.001, 44.5% vs. 37.6%, p < 0.0001), respectively. MF cycles also demonstrated higher LBR and CLBR with FET (52.3% vs. 44.2%, p < 0.001, 81.2% vs. 68.9%, p < 0.0001), respectively. MLR demonstrated that in DOR cycles, initial FET was associated with greater chance of live birth in age groups ≥ 35yo (p < 0.01), with aOR of live birth increasingly considerably for those > 42yo (aOR 2.63, p < 0.0001). CONCLUSIONS: Overall LBR and CLBR were greater for first FET than fresh transfers with incremental increases in odds of live birth with advancing age, suggesting the presence of a more favorable age-related change in endometrial receptivity present in frozen-thawed cycles. For both DOR and MF cycles, LBR and CLBR after primary transfer were greater for first FET than fresh. However, this was particularly evident in older ages for DOR cycles. This suggests that supraphysiologic stimulation in older DOR cycles may be detrimental to endometrial receptivity, which is in part corrected for in FET cycles.

Live birth rates following individualized dosing algorithm of follitropin delta in a long GnRH agonist protocol.

PURPOSE: To explore the efficacy and safety of individualized follitropin delta dosing, based on serum anti-Müllerian hormone (AMH) concentration and bodyweight, in a long gonadotropin-releasing hormone (GnRH) agonist protocol. METHODS: Clinical outcomes after one treatment cycle are reported in women with AMH: 5-35 pmol/L. Oocytes were inseminated by intracytoplasmic sperm injection, blastocyst transfer was on Day 5 and remaining blastocysts were cryopreserved. Data collection included live births and neonatal health follow-up for all fresh/frozen transfers performed within one year after treatment allocation. RESULTS: In total, 104 women started stimulation, of whom 101 had oocyte recovery and 92 had blastocyst transfer. The average daily dose of follitropin delta was 11.0 ± 1.6 µg and the duration of stimulation was 10.3 ± 1.6 days. The mean number of oocytes was 12.5 ± 6.4, the mean number of blastocysts was 5.1 ± 3.4, and 85% had at least one good-quality blastocyst. Following mostly single blastocyst transfer (95%), the ongoing pregnancy rate was 43%, the live-birth rate was 43%, and the cumulative live-birth rate was 58% per started stimulation. There were 6 cases of early OHSS (5.8%) graded as mild (n = 3) and moderate (n = 3) and 6 cases of late OHSS (5.8%) graded as moderate (n = 3) and severe (n = 3). CONCLUSION: In this first evaluation of the individualized follitropin delta dosing in a long GnRH agonist protocol, the cumulative live-birth rate was high. A randomized trial comparing follitropin delta in a long GnRH agonist protocol versus in a GnRH antagonist protocol should provide further insight into the efficacy and safety of this treatment option. TRIAL REGISTRATION NUMBER: NCT03564509; June 21, 2018.

Cumulative live birth rates with autologous oocytes plateau with fewer number of cycles for each year of age > 42.

OBJECTIVE: To disaggregate the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) age category of " > 42" and compare age-stratified cumulative live birth rates (CLBR) > 42 years old. DESIGN: Retrospective cohort study of autologous linked ART cycles. SETTING: United States (US) National ART Database. PATIENT(S): Women > 42 years old without a history of prior ART cycles who underwent ART between 2014-2020 as reported to the SART CORS database. INTERVENTION(S): Disaggregate the SART CORS age category of " > 42" into age-stratified cumulative live birth rates (CLBR). MAIN OUTCOME MEASURE(S): Age-stratified cumulative live birth rates (CLBR) for women ≥ 43 years old. RESULTS: Between 2014-2020, 24,650 women > 42 years old without history of prior ART underwent 58,132 cycles, resulting in 1,982 live births. Women ages 43, 44, 45, 46, 47, 48, 49, ≥ 50 achieved maximal CLBR of 9.7%, 8.6%, 5.0%, 3.6%, 2.5%, 1.5%, 2.7%, 1.3%, respectively. CLBR for women between 43-45 were significantly higher compared to those 46 and older (p < 0.05). Among women 46 and older, CLBR were not significantly different. Women ages 43 and 44 did not exhibit a significant increase in CLBR beyond the 5th cycle. Age 45 and 46 reached CLBR plateau by the 3rd cycle. Age ≥ 47 CLBR plateaued after the first cycle. After adjusting for age, race/ethnicity, BMI, nulliparity, etiology of infertility, number of oocytes retrieved, embryos transferred, blastocyst transfer, use of ICSI, PGT, and ART treatment cycle number, there was no association between markers of ovarian reserve (day 3 FSH and random AMH levels) and live birth for women > 42. CONCLUSIONS: While CLBR of autologous cycles from women 42 or younger generally plateau by cycle number 5, age-stratified cycles from women > 42 plateau after fewer cycles to maximize CLBR. Patient and physician expectations for maximum CLBR beyond 42 may be practically based on fewer planned cycles before reaching an age-specific CLBR plateau than may have been previously expected.

Effect of the ratios of estradiol increase on the outcome of in vitro fertilization-embryo transfer with antagonist regimens: a single center retrospective cohort study.

BACKGROUND: The outcome of in vitro fertilization-embryo transfer (IVF) is often determined according to follicle and estradiol levels following gonadotropin stimulation. In previous studies, although most of them analyzed the estrogen level from ovaries or the average estrogen level of a single follicle, there was no study on the ratio of estrogen increase, which was also correlated with pregnancy outcomes in the clinic. This study aimed to make timely adjustments to follow-up medication to improve clinical outcomes based on the potential value of estradiol growth rate. METHODS: We comprehensively analyzed estrogen growth during the entire ovarian stimulation period. Serum estradiol levels were measured on the day of gonadotropin treatment (Gn1), five days later (Gn5), eight days later (Gn8), and on the trigger day (HCG). This ratio was used to determine the increase in estradiol levels. According to the ratio of estradiol increase, the patients were divided into four groups: A1 (Gn5/Gn1 ≤ 6.44), A2 (6.44 < Gn5/Gn1 ≤ 10.62), A3 (10.62 < Gn5/Gn1 ≤ 21.33), and A4 (Gn5/Gn1 > 21.33); B1 (Gn8/Gn5 ≤ 2.39), B2 (2.39 < Gn8/Gn5 ≤ 3.03), B3 (3.03 < Gn8/Gn5 ≤ 3.84), and B4 (Gn8/Gn5 > 3.84). We analyzed and compared the relationship between data in each group and pregnancy outcomes. RESULTS: In the statistical analysis, the estradiol levels of Gn5 (P = 0.029, P = 0.042), Gn8 (P < 0.001, P = 0.001), and HCG (P < 0.001, P = 0.002), as well as Gn5/Gn1 (P = 0.004, P = 0.006), Gn8/Gn5 (P = 0.001, P = 0.002), and HCG/Gn1 (P < 0.001, P < 0.001) both had clinical guiding significance, and lower one significantly reduced the pregnancy rate. The outcomes were positively linked to groups A (P = 0.036, P = 0.043) and B (P = 0.014, P = 0.013), respectively. The logistical regression analysis revealed that group A1 (OR = 0.376 [0.182-0.779]; P = 0.008*, OR = 0.401 [0.188-0.857]; P = 0.018*) and B1 (OR = 0.363 [0.179-0.735]; P = 0.005*, OR = 0.389 [0.187-0.808]; P = 0.011*) had opposite influence on outcomes. CONCLUSION: Maintaining a serum estradiol increase ratio of at least 6.44 on Gn5/Gn1 and 2.39 on Gn8/Gn5 may result in a higher pregnancy rate, especially in young people.

Presence of endometrioma decreased blastocyst formation rate but not impair Assisted Reproductive Technology (ART) outcome.

PURPOSE: This study aims to assess the impact of endometrioma on patients who undergo ART treatment due to endometriosis. METHODS: A retrospective study was conducted on women ≤ 40 years of age who underwent ART treatment at an academic medical center between January 2014 and December 2020. Two-hundred-and-eight women had received IVF/ICSI treatment due to endometriosis and there were 89 patients presence of endometrioma. Patients were further divided into primary endometrioma, recurrent endometrioma and those having received cystectomy for endometrioma prior to IVF/ICSI. The control group included 624 infertile women without endometriosis. RESULTS: In the endometrioma subgroup (B) the blastocyst formation rate was significantly lower when compared with the endometriosis (A) and control groups (C). The cumulative live birth rates (CLBRs) (60.5% versus 49.4% versus 56.9%, p = 0.194 in A versus B, p = 0.406 in A versus C, p = 0.878 in B versus C) were comparable. Multiple logistic regression analysis revealed that female age, total FSH dose and blastocyst formation rate were the significant variables in predicting CLBR (OR 0.89, CI 0.80-0.99, p < 0.025, OR 0.68 CI 0.53-0.88, p = 0.003 and OR 30.04, CI 9.93-90.9, p < 0.001, respectively). The CLBRs were comparable at 47.1%, 60% and 57.9% in the primary endometrioma, s/p cystectomy and recurrent endometrioma group. CONCLUSION: Although the blastocyst formation rate was lower in the endometrioma group, CLBR was not worse than those who were in the endometriosis or control group. Cystectomy for endometrioma did not alter IVF/ICSI outcomes if the ovarian reserve was comparable. Recurrent endometrioma did not worsen IVF/ICSI outcomes than primary endometrioma.

Cumulative live birth rates for women returning to ART treatment for a second ART-conceived child.

STUDY QUESTION: What are the success rates for women returning to ART treatment in the hope of having a second ART-conceived child. SUMMARY ANSWER: The cumulative live birth rate (LBR) for women returning to ART treatment was between 50.5% and 88.1% after six cycles depending on whether women commenced with a previously frozen embryo or a new ovarian stimulation cycle and the assumptions made regarding the success rates for women who dropped-out of treatment. WHAT IS KNOWN ALREADY: Previous studies have reported the cumulative LBR for the first ART-conceived child to inform patients about their chances of success. However, most couples plan to have more than one child to complete their family and, for that reason, patients commonly return to ART treatment after the birth of their first ART-conceived child. To our knowledge, there are no published data to facilitate patient counseling and clinical decision-making regarding the success rates for these patients. STUDY DESIGN, SIZE, DURATION: A population-based cohort study with 35 290 women who commenced autologous (using their own oocytes) ART treatment between January 2009 and December 2013 and achieved their first treatment-dependent live birth from treatment performed during this period. These women were then followed up for a further 2 years of treatment to December 2015, providing a minimum of 2 years and a maximum of 7 years of treatment follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cycle-specific LBR and cumulative LBR were calculated for up to six complete ART cycles (one ovarian stimulation and all associated transfers). Three cumulative LBR were calculated based on the likelihood of success in women who dropped-out of treatment (conservative, optimal and inverse probability-weighted (IPW)). A multivariable logistic regression model was used to predict the chance of returning to ART treatment for a second ART-conceived child, and a discrete time logistic regression model was used to predict the chance of achieving a second ART-conceived child up to a maximum of six complete cycles. The models were adjusted for patient characteristics and previous and current treatment characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Among the women who had their first ART-conceived live birth, 15 325 (43%) returned to treatment by December 2015. LBRs were consistently better in women who recommenced treatment with a previously frozen embryo, compared to women who underwent a new ovarian stimulation cycle. After six complete cycles, plus any surplus frozen embryos, the cumulative LBR was between 60.9% (95% CI: 60.0-61.8%) (conservative) and 88.1% (95% CI: 86.7-89.5%) (optimal) [IPW 87.2% (95% CI: 86.2-88.2%)] for women who recommenced treatment with a frozen embryo, compared to between 50.5% (95% CI: 49.0-52.0%) and 69.8% (95% CI: 67.5-72.2%) [IPW 68.1% (95% CI: 67.3-68.9%)] for those who underwent a new ovarian stimulation cycle. The adjusted odds of a second ART-conceived live birth decreased for women ≥35 years, who waited at least 3 years before returning to treatment, or who required a higher number of ovarian stimulation cycles or double embryo transfer to achieve their first child. LIMITATIONS, REASONS FOR CAUTION: Our estimates do not fully account for a number of individual prognostic factors, including duration of infertility, BMI and ovarian reserve. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to report success rates for women returning to ART treatment to have second ART-conceived child. These age-specific success rates can facilitate individualized counseling for the large number of patients hoping to have a second child using ART treatment. STUDY FUNDING/COMPETING INTEREST(S): No funding was received to undertake this study. R. Paul and O. Fitzgerald have nothing to declare. D. Lieberman reports being a fertility specialist and receiving non-financial support from MSD and Merck outside the submitted work. C. Venetis reports being a fertility specialist and receiving personal fees and non-financial support from MSD, personal fees and non-financial support from Merck Serono and Beisins and non-financial support from Ferring outside the submitted work. G.M. Chambers reports being a paid employee of the University of New South Wales, Sydney (UNSW) and Director of the National Perinatal Epidemiology and Statistics Unit (NPESU), UNSW. The Fertility Society of Australia (FSA) contracts UNSW to prepare the Australian and New Zealand Assisted Reproductive Technology Database (ANZARD) annual report series and benchmarking reports. TRIAL REGISTRATION NUMBER: NA.

Success rates in minimal stimulation cycle IVF with clomiphene citrate only.

PURPOSE: To determine age-adjusted overall success rates for patients undergoing clomiphene citrate only minimal stimulation cycle (mini) in vitro fertilization (IVF) without any gonadotropin administration. METHODS: Eight hundred thirty-nine women (mean age: 38.4 ± 0.1 years; 2488 cycles) underwent clomiphene citrate only mini-IVF. Their first oocyte retrieval was between January 2009 and December 2009, with follow-up until December 2014. The cumulative live birth rate (CLBR) per oocyte retrieval cycle started and live birth rate per oocyte was retrospectively analyzed. The basic CLBR was calculated as the number of women who achieved a live birth divided by the total number of women who started oocyte retrieval. RESULTS: The mean number of oocytes retrieved was 1.5. The basic CLBRs for all ages after the first and third cycles were 22.6% and 39.2%, respectively. For ≤ 34 years, 35-37 years, 38-40 years, 41-42 years, and ≥ 43 years, CLBRs after the first and third cycles were 42.5% and 70.1%, 32.9% and 49.1%, 20.0% and 38.6%, 12.6% and 25.2%, and 4.4% and 8.8%, respectively. These rates had a significant relationship with age (P < 0.01). The LBR per oocyte for all ages was 9.6%. CONCLUSION: Acceptable overall IVF success rates can be achieved in clomiphene citrate only mini-IVF, as well as acceptable LBR. The CLBRs and LBRs per oocyte are evidently influenced by women's age.

Assisted reproductive technology (ART) cumulative live birth rates following preimplantation genetic diagnosis for aneuploidy (PGD-A) or morphological assessment of embryos: A cohort analysis.

BACKGROUND: Preimplantation genetic diagnosis for aneuploidy (PGD-A) for all 24 chromosomes improves implantation and clinical pregnancy rates per single assisted reproductive technology (ART) cycle. However, there is limited data on the live-birth rate of PGD-A over repeated cycles. AIM: To assess the cumulative live-birth rates (CLBR) of PGD-A compared with morphological assessment of embryos of up to three 'complete ART cycles' (fresh plus frozen/thaw cycles) in women aged 37 years or older. MATERIALS AND METHODS: A retrospective cohort study of ART treatments undertaken by ART-naïve women at a large Australian fertility clinic between 2011 and 2014. Cohorts were assigned based on the embryo selection method used in their first fresh cycle [PGD-A, n = 110 women (PGD-A group); morphological assessment of embryos, n = 1983 women (control group)]. CLBR, time to clinical pregnancy and cycles needed to achieve a live birth were measured over multiple cycles. RESULTS: Compared to the control group, the PGD-A group achieved a higher per cycle live-birth rate (14.47% vs 9.12%, P < 0.01), took a shorter mean time to reach a clinical pregnancy leading to a live-birth (104.8 days vs 140.6 days, P < 0.05) and required fewer cycles to achieve a live-birth (6.91 cycles vs 10.96 cycles, P < 0.01). However, after three 'complete ART cycles', the CLBR was comparable for the two groups (30.90% vs 26.77%, P = 0.34). CONCLUSION: This is the first study to assess the effectiveness of PGD-A over multiple ART cycles. These real-world findings suggest that PGD-A leads to better outcomes than using morphological assessment alone in women of advanced maternal age.

Cumulative live birth rates following intrauterine insemination using donor and husband sperm in different age groups: A cohort study of 10 415 insemination cycles.

OBJECTIVES: To assess the age-specific cumulative live birth rates (CLBRs) in intrauterine insemination (IUI) cycles using either donor or husband sperm, and to investigate the impact of sperm sources on IUI success among women within the same age group. METHODS: This retrospective cohort study comprised women who underwent IUI with donor sperm (IUI-D) or husband sperm (IUI-H) from 2017 to 2021. The women were stratified based on their age at the initiation of insemination into four categories: <35, 35-37, 38-39 and ≥40 years. RESULTS: A total of 5253 women undergoing 10 415 insemination cycles (3354 with IUI-D and 7061 with IUI-H) were included. The CLBRs decreased significantly with increasing maternal age within donor and husband insemination groups (P < 0.001). In the IUI-D group, the crude CLBRs were 61.50% in women aged <35, 48.91% in 35-37, 24.14% in 38-39 and 11.76% in the ≥40-year age category, respectively. The corresponding rates in the IUI-H group were 27.62%, 22.96%, 13.73% and 6.90%, respectively. Within the <35 and 35-37-year age categories, the CLBRs were significantly higher following IUI-D cycles compared to IUI-H cycles, with hazard ratios (HR) of 1.85 (1.68-2.04) and 1.69 (1.16-2.47), respectively. However, within the 38-39 and ≥40-year age categories, both IUI-D and IUI-H resulted in comparable low CLBRs, with HRs of 1.91 (0.77-4.76) and 1.80 (0.33-9.86), respectively. CONCLUSION: Advanced maternal age affects the whole process of fertility. Therefore, it could be reasonable to limit the number of IUI performed in women aged 40 years and older, even in couple using donor sperm for reproduction.

Effect of time since vasectomy on live birth rate of TESE‒ICSI egg donation cycles and male-related prognostic factors.

BACKGROUND: Vasectomy is a widely used method of contraception. However, some men may have the desire to become biological fathers again after a period. OBJECTIVE: To explore the effect of time since vasectomy and different male comorbidities on live birth rates from intracytoplasmic sperm injection cycles using donated oocytes by using testicular spermatozoa obtained by testicular sperm extraction. MATERIALS AND METHODS: This was a retrospective study of 123 couples who underwent a testicular sperm extraction‒intracytoplasmic sperm injection cycle after vasectomy using donated oocytes. Subjects were divided into groups according to time since vasectomy and the male risk factor evaluated. The main outcomes measured were live birth rate per embryo transfer, per oocyte donation cycle, and per couple. We assessed the cumulative live birth rate according to the time since vasectomy and considered male comorbidities: body mass index, hypertension, diabetes mellitus, dyslipidemia, and smoking. RESULTS: The overall live birth rate per couple was 59.3% (50.6-68.0). Considering the number of embryo transfer and oocyte donation cycle, the live birth rates were 34.1% (27.8-40.4) and 44.5% (36.9-52.1), respectively. The live birth rate according to time since vasectomy was not statistically different between groups. Consequently, the cumulative live birth rate was similar between the different interval times when considering one to eight embryo transfers (p = 0.74). No statistical differences in live birth rate and cumulative live birth rate were found between groups clustered according to male body mass index, smoking, hypertension, and dyslipidemia. However, diabetic male patients had a significantly lower rate of live birth rate per couple (22.2% [4.94-49.4]) than non-diabetic patients did (62.7% [53.7-71.8]) (p = 0.03), but not in their cumulative live birth rate. CONCLUSIONS: The time since vasectomy seems to have no detrimental effects on the live birth rate and cumulative live birth rate in testicular sperm extraction‒intracytoplasmic sperm injection cycles with donated oocytes. Male diabetes negatively affects the overall live birth rate per couple, but not the cumulative live birth rate. These results could be useful for multidisciplinary patient-tailored counseling, regarding the chance of having a pregnancy and facilitating the decision-making process of the fertility specialists.

Factors affecting the reproductive outcome in reciprocal translocation carriers undergoing preimplantation genetic testing for structural rearrangements (PGTSR).

OBJECTIVE: To investigate the reproductive outcomes of balanced reciprocal translocation carriers and evaluate the association between the number of metaphase-II oocytes retrieved and cumulative live birth rates (LBRs). METHODS: This retrospective analysis included 344 preimplantation genetic testing (PGT) for structural rearrangement cycles of 281 couples with balanced reciprocal translocations between January 2018 and January 2021. All patients included in the analysis had either delivered a baby or had used all their embryos after one stimulation cycle. All women were followed up for at least 2 years. RESULTS: After ovarian stimulation and oocyte fertilization, 44.2% of PGT for structural rearrangements cycles achieved a live birth. Carrier's sex and female age did not affect the cumulative LBR of reciprocal translocation carriers. Cumulative LBRs steadily increased with the number of oocytes, reaching 64% when >20 oocytes were retrieved. The cutoff values for achieving at least one live birth were 9.5 metaphase-II (MII) oocytes and 3.5 biopsied embryos. CONCLUSION: Couples with reciprocal translocations have lower transferable embryo rates and cumulative LBRs. The MII oocytes retrieved may be a crucial factor for cumulative LBRs. A high ovarian response may further increase cumulative LBRs, but avoidance of ovarian hyperstimulation syndrome or other iatrogenic complications should be considered.

Cumulative live birth rates and birth outcomes after IVF/ICSI treatment cycles in young POSEIDON patients: A real-world study.

Objective: The aim of this study was to describe the cumulative live birth rates (CLBRs) of young women with or without low prognosis according to the POSEIDON criteria after IVF/ICSI cycles and to investigate whether the diagnosis of low prognosis increases the risk of abnormal birth outcomes. Design: Retrospective study. Setting: A single reproductive medicine center. Population: From January 2016 to October 2020, there were 17,893 patients (<35 years) involved. After screening, 4,105 women were included in POSEIDON group 1, 1,375 women were included in POSEIDON group 3, and 11,876 women were defined as non-POSEIDON. Interventions: Baseline serum AMH level was measured on the D2-D3 of menstrual cycle before IVF/ICSI treatment. Main outcome measures: Cumulative live birth rate (CLBR), birth outcomes. Results: After four stimulation cycles, the CLBRs in POSEIDON group 1, POSEIDON group 3, and non-POSEIDON group reached 67.9% (95% CI, 66.5%-69.3%), 51.9% (95% CI, 49.2%-54.5%), and 79.6% (95% CI, 78.9%-80.3%), respectively. There was no difference in gestational age, preterm delivery, cesarean delivery, and low birth weight infants between the three groups, but macrosomia was significantly higher in non-POSEIDON group, after adjusting for maternal age and BMI. Conclusions: The POSEIDON group shows lower CLBRs than the non-POSEIDON group in young women, while the risk of abnormal birth outcomes in the POSEIDON group will not increase.

Retrospective Analysis of Meiotic Segregation Pattern and Reproductive Outcomes in Blastocysts from Robertsonian Preimplantation Genetic Testing Cycles.

In this retrospective study, 120 heterozygous Robertsonian translocation carriers undergoing preimplantation genetic testing (PGT) were included, between January 2018 and September 2021. Meiotic segregation patterns of 462 embryos from 51 female carriers and 69 male carriers were analyzed according to chromosome type, carrier's sex, and female age. The proportion of alternate embryos in female carriers was slightly lower than that in male carriers [P < 0.001, odds ratio (OR) = 0.512]. By contrast, no difference was observed among Rob (13;14), Rob (14;21), and rare RobT groups. Stratification analysis of female carriers' age doses showed no significant increase in unbalanced chromosomal abnormalities. Reproductive outcomes of 144 frozen-thawed cycles were analyzed. All 144 blastocysts were transferred, and there were no significant differences in the clinical pregnancy rates per transfer (CPR), miscarriage rates (MR), live birth rates per transfer (LBR), and cumulative live birth rates between female carriers and male carriers. In addition, couples in Rob (13;14), Rob (14;21), and rare RobTs groups had comparative clinical pregnancy rates per transfer (CPR), miscarriage rates (MR), live birth rates per transfer (LBR), and cumulative live birth rates. Our study demonstrated that the meiotic segregation pattern of Robertsonian translocations carriers is associated with the carrier's sex, but not the carrier's translocation type and female age. In addition, the sex of translocation carriers only affects the meiotic segregation pattern but does not influence the subsequent viability of normal embryos and live birth.

Chronic poor healing wounds of post cesarean scar diverticulum: Altered angiogenesis and immunobiology.

Cesarean section (CS) scar diverticula (CSD) is an important cause impede further fecundity, with rather complicated pathophysiologic mechanisms and unclear etiopathogenesis. In this study, we detect the influences of CSD on the pregnancy outcomes in in-vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI) embryo transfer (ET) cycles, and further explore the mechanisms involved based on histopathology and immunology differences in endometrium between CSD and vaginal birth (VB) women. The CS group had significantly lower CLBR compared to NCS group. Histopathological analysis showed that the higher prevalent of CE is accompanied by excessive fibroblast proliferation at the lower segment of uterus and significantly exaggerated vascular proliferation in situ. Intrauterine inflammatory cytokines including IL-1α, IL-1ß, IL-6, IL-8, TNF-α and SDF-1α were also increased in CSD group. The present data suggests impaired fecundity in CSD women undergoing IVF/ICSI treatment. Although the causal relationship is ambiguous, the potential mechanisms may involve persistent inflammatory response in the uterine cavity, active vascular proliferation accompanied with increased fibrosis which are responsible for poor chronic wound healing of CSD.

Comparison of the cumulative live birth rates after 1 in vitro fertilization cycle in women using gonadotropin-releasing hormone antagonist protocol vs. progestin-primed ovarian stimulation: a propensity score-matched study.

OBJECTIVE: To determine whether gonadotropin-releasing hormone (GnRH) antagonist protocol can improve cumulative live birth rates (CLBRs) and shorten the time to live birth (TTLB) in unselected patients compared with progestin-primed ovarian stimulation (PPOS). DESIGN: A propensity score-matched retrospective cohort study design. SETTING: Tertiary-care academic medical center. PATIENT(S): A total of 6,520 women with infertility aged 20-50 years were included. INTERVENTION(S): Patients underwent either the GnRH antagonist protocol (n = 5,004) or PPOS (n = 1,516) on the basis of the assessment of the attending physicians. One-to-one propensity score matching was performed with a caliper of 0.02. Women who were not matched were excluded from the analyses. MAIN OUTCOME MEASURE(S): The CLBR of which the ongoing status had to be achieved within 22 months from the day of ovarian stimulation and TTLB. RESULT(S): Each group comprised 1,424 couples after propensity score matching, and the baseline demographic characteristics of the couples after matching were comparable between the 2 groups. The cycle cancellation rate was significantly lower in the GnRH antagonist group than in the PPOS group (12.9% vs. 19.6%). The implantation rate, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate per transfer were comparable between the 2 groups. However, CLBRs after 1 complete IVF cycle were significantly higher in the GnRH antagonist group than in the PPOS group (36.0% vs. 32.2%; Risk ratio = 1.12; 95% confidence interval [CI], 1.01-1.24). The average TTLB was significantly shorter in the GnRH antagonist group than in the PPOS group (9.3 months vs. 12.4 months). Using the Kaplan-Meier analysis, the cumulative incidence of ongoing pregnancy leading to live birth was significantly higher in the GnRH antagonist group than in the PPOS group (85.1% vs. 66.1%, Log-rank test). A Cox proportional hazard model revealed that women who underwent the antagonist protocol were 2.32 times more likely to achieve a live birth than those who used PPOS (hazard ratio [HR] = 2.32; 95% CI, 1.91-2.83). Subgroup analysis revealed that women who used the antagonist protocol were more likely to achieve a live birth than women who used PPOS across the 3 antral follicle count (AFC) strata (AFC ≤ 5, AFC 6-15, and AFC > 15), 2 age strata (<35 and ≥35 years), and first cycle or repeated cycle. The difference was greatest among women whose AFC was ≤5 and who were aged ≥35 years, effectively becoming smaller in the group with high ovarian reserve and younger age. CONCLUSION(S): In unselected women undergoing IVF, the GnRH antagonist protocol was associated with a higher CLBR and a shorter TTLB compared with PPOS.

Sperm deoxyribonucleic acid fragmentation (by terminal deoxynucleotidyl transferase biotin dUTP nick end labeling assay) does not impair reproductive success measured as cumulative live birth rates per donor metaphase II oocyte used.

OBJECTIVE: To better study the effect of sperm deoxyribonucleic acid fragmentation (SDF) on intracytoplasmic sperm injection (ICSI) outcomes from an ovum donation program by assessing the cumulative live birth rates (CLBRs) per number of embryo transfers (ETs), embryos replaced (EmbR), and metaphase II (MII) oocytes required in consecutive treatments to achieve the first newborn. DESIGN: A multicenter retrospective cohort study was conducted, and the Kaplan-Meier survival curves were generated to calculate the CLBR with regard to the SDF degree. SETTING: Private university-affiliated in vitro fertilization centers. PATIENT(S): Data from 864 couples using donated eggs and undergoing ICSI from 2000 to 2019 were analyzed. Sperm deoxyribonucleic acid fragmentation was measured using terminal deoxynucleotidyl transferase biotin dUTP nick end labeling assay on their ejaculated sperm. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth rate (LBR) per first ET and per all consecutive ETs within the same patient and CLBR per ET, per EmbR, and per MII oocyte used considering the SDF level. RESULT(S): A total of 1,903 ICSI cycles were considered, encompassing 6,340 donated oocytes, 2,543 embryos, and 1,145 ETs. Comparing ≤15% SDF (low) with >15% SDF (high) or by 10% SDF ranges, the LBRs per first ET and per all ETs did not significantly differ. The Kaplan-Meier curves of the CLBR per ET, per EmbR, and per donor oocyte consumed were similar between the SDF groups evaluated. CONCLUSION(S): Elevated SDF does not reduce the LBR or cumulative probability to obtain a child when calculated per ET, per EmbR, and per donated MII oocyte used in couples undergoing ICSI cycles.

Cost-effectiveness of freeze-all policy - A retrospective study based upon the outcome of cumulative live births.

OBJECT: We have previously reported that cumulative live birth rates (CLBRs) are higher in the freeze-all group compared with controls (64.3% vs. 45.8%, p = 0.001). Here, we aim to determine if the freeze-all policy is more cost-effective than fresh embryo transfer followed by frozen-thawed embryo transfer (FET). MATERIALS AND METHODS: The analysis consisted of 704 ART (Assisted reproductive technology) cycles, which included in IVF (In vitro fertilisation) and ICSI (Intra Cytoplasmic Sperm Injection) cycles performed in Taichung Veterans General Hospital, Taiwan between January 2012 and June 2014. The freeze-all group involved 84 patients and the fresh Group 625 patients. Patients were followed up until all embryos obtained from a single controlled ovarian hyper-stimulation cycle were used up, or a live birth had been achieved. The total cost related to treatment of each patient was recorded. The incremental cost-effectiveness ratio (ICER) was based on the incremental cost per couple and the incremental live birth rate of the freeze-all strategy compared with the fresh ET strategy. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were performed. RESULTS: The total treatment cost per patient was significantly higher for the freeze-all group than in the fresh group (USD 3419.93 ± 638.13 vs. $2920.59 ± 711.08 p < 0.001). However, the total treatment cost per live birth in the freeze-all group was US $5319.89, vs. US $6382.42 in the fresh group. CEAC show that the freeze-all policy was a cost-effective treatment at a threshold of US $2703.57 for one additional live birth. Considering the Willingness-to-pay threshold per live birth, the probability was 60.1% at the threshold of US $2896.5, with the freeze-all group being more cost-effective than the fresh-ET group; or 90.1% at the threshold of $4183.8. CONCLUSION: The freeze-all policy is a cost-effective treatment, as long as the additional cost of US $2703.57 per additional live birth is financially acceptable for the subjects.

Cumulative live birth rates do not increase after 4 complete cycles in women with poor ovarian response: a retrospective study of 1,825 patients.

OBJECTIVE: To investigate whether the cumulative clinical pregnancy rates (CCPR) and cumulative live birth rates (CLBR) increase as the oocyte retrieval cycle increases in women with poor ovarian response. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENTS: Women diagnosed of poor ovarian response (POR) according to the Bologna criteria and who completed in vitro fertilization or intracytoplasmic sperm injection cycles between January 2014 and December 2018. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The conservative and optimistic estimations of CCPR and CLBR. RESULTS: The conservative and optimistic estimates of CCPR peaked at the 6th complete cycle, reaching 36.44% and 71.61%, respectively. However, the conservative and optimistic estimates of CLBR peaked at the 4th complete cycle, reaching 20.22% and 38.31%, respectively. The live birth rate per complete cycle of mild stimulation protocol was comparable to other protocols after adjusting for the confounding factors. For patients ≤35 years, the live birth rate per complete cycle of progestin-primed ovarian stimulation (adjusted odds ratio = 0.51, 95% confidence interval: 0.30-0.87) and gonadotropin-releasing hormone antagonist protocol (adjusted odds ratio=0.45, 95% confidence interval: 0.24-0.81) were significantly lower than that of the mild stimulation. CONCLUSIONS: It is not advisable to initiate more than four complete cycles for POR patients since CLBR do not increase after that. For POR patients ≤35 years, the live birth rate per complete cycle increased in women with mild stimulation protocol.

Independent Variables for Determining the Cumulative Live Birth Rates of Aged Patients with Polycystic Ovary Syndrome or Tubal Factor Infertility: A Retrospective Cohort Study.

Objective: To assess whether women of advanced age (≥35 years) with polycystic ovary syndrome (PCOS) have the same cumulative live birth rate (CLBR) as their age-matched controls with tubal factor infertility and to determine the influencing factors on the CLBRs of aged women. Design: A retrospective cohort study. Setting and Population: A total of 160 women of advanced age (≥35 years) with PCOS and 1073 women with tubal factor infertility were included in our study. All patients underwent their first fresh cycles and subsequent frozen cycles within in one year in our centre from 2015 to 2020. Methods: To determine independent influencing factors on the CLBRs of these aged patients, a multivariable Cox regression model of CLBR according to the transfer cycle type was constructed. Main outcome measure(s): CLBRs. Result: The Cox regression model of the CLBRs indicated that there was no significant difference between the PCOS group and the tubal infertility group in terms of advanced age (HR, 0.95; 95% CI, 0.71-1.27, P=0.732). The CLBR significantly decreased for women of advanced reproductive age up to 37 years of age (HR, 0.46; 95% CI, 0.39-0.56, P<0.001). The CLBR increased by 63% when more than ten oocytes were retrieved (HR, 1.63; 95% CI, 1.34-1.98, P<0.001). Patients with an AMH level above 32.13pmol/l were likely to have a 72%(HR, 1.72; 95% CI, 1.08-2.73, = 0.023) and 34% (HR, 1.34; 95% CI, 1.07-1.68, P=0.010)improvement in CLBR compared to those with an AMH below 7.85pmol/l and 7.85-32.12pmol/l, respectively. Conclusion: Despite the higher number of oocytes retrieved in PCOS patients, the reproductive window is not extended for PCOS patients compared with tubal factor infertility patients. Age, AMH and the number of oocytes retrieved play crucial roles in the CLBRs of patients of advanced age (≥35 years).