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

ObjectiveTo 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.DesignA retrospective cohort study.Setting and PopulationA 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.MethodsTo 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.ResultThe 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.ConclusionDespite 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).

Cumulative Live Birth Rates for Low-Prognosis Women Over 5 Years or 9 Frozen-Thawed Embryo Transfer Cycles

Background: For heterogeneous populations of low-prognosis women, it remains unclear as to how long individuals should continue undergoing ART when attempting to have a baby, as there have been insufficient studies to date tracking the cumulative live birth rates (CLBRs) for these women over the entire course of their ART treatment, particularly over extended time periods. Methods: This was a retrospective analysis of 17,698 women at a tertiary care academic medical center who had begun undergoing IVI/ICSI cycles using a PPOS approach between January 2013 and January 2019. Low-prognosis patients were stratified into four groups based upon POSEIDON criteria, with patients exhibiting normal or high ovarian reserves and response to stimulation (defined as AFC ≥5, >9 oocytes retrieved) being included as controls (group 5). The CLBR within 5 years or 9 FET cycles from the OPU day of the first cycle was the primary endpoint for this study, including all repetitive oocyte retrieval cycles and subsequent FET cycles. Optimistic and conservative approaches were used for the analysis of CLBRs and the depiction of cumulative incidence curves.Results: Under both optimistic and conservative model analyses, patients in group 5 exhibited the highest CLBR within 5 years or 9 FET cycles, followed by POSEIDON group 1, group 3, group 2, and group 4. Upward trends in CLBRs were evident across the five groups with the prolongation of time or an increase in FET cycle counts. Within the first 2 years or 3 FET cycles, the CLBRs rose rapidly, followed by more moderate increases over the following 2-3.5 years or 4-6 cycles, with the patients in group 3 and group 4 exhibiting the most obvious improvements. Patients in all groups reached a CLBR plateau after 3.5 years or 6 FET cycles.Conclusions: All low-prognosis women should undergo ART treatment for a minimum of 2 years or 3 FET cycles, and exhibit better outcomes when extending ART treatment to 3.5 years or 6 FET cycles (particularly for POSEIDON groups 3 and 4), but should consider ceasing further treatment thereafter due to a lack of apparent benefit.

Comparison of the C Umulative Live Birth Rates After One ART Cycle Including All Subsequent Frozen–thaw Cycles in Women Undergoing IVF Using Progestin Primed Ovarian Stimulation Versus Long GnRH Agonist Protocol

Background: The efficacy and reproductive outcomes of progestin primed ovarian stimulation protocol (PPOS) were previously compared to rarely used ovarian stimulation protocol and also the live birth rate were reported by per embryo transfer rather than cumulative live birth rates (CLBRs). Does the use of PPOS improve the cumulative live birth rates (CLBRs) and shorten time to live birth when compared to long GnRH agonist protocol in women with normal ovarian reserve?Methods: A retrospective cohort study was designed to include women aged<40 with normal ovarian reserve (regular menstrual cycles, FSH <10 IU/L, antral follicle count >5) undergoing IVF from January 2017 to December 2019. The primary outcome was cumulative live birth rates (CLBRs) within 18 months from the day of ovarian stimulation.Results: A total of 995 patients were analyzed. They used either PPOS (n=509) or long GnRH agonist (n=486) protocol at the discretion of the attending physicians. Both groups had almost comparable demographic and cycle stimulation characteristics except for duration of infertility which was shorter in the PPOS group. In the GnRH agonist group 372 cases (77%) completed fresh embryo transfer, resulting into 218 clinical pregnancies and 179 live birth. The clinical pregnancy rate, ongoing pregnancy, and live birth per transfer were 58.6%, 54.0%, 53.0% respectively. In the PPOS, no fresh transfer was carried out. During the study period, the total number of initiated FET cycles with thawed embryos was 665 in the PPOS group and 259 in the long agonist group. Of all FET cycles, a total of 206/662 (31.1%) cycles resulted in a live birth in the PPOS group versus 110/257 (42.8%) in the long agonist group (OR: 0.727; 95% CI: 0.607–0.871; p<0.001) .The implantation rate of total FET cycles was also lower in the PPOS group compared with that in the agonist group 293/1004 (29.2%) and 157/455 (34.5%) (OR: 0.846; 95% CI: 0.721–0.992; p= 0.041). Cumulative live birth rates after one complete IVF cycle including fresh and subsequent frozen embryo cycles within 18 months follow up were significantly lower in the PPOS group compared that in the long agonist group 206/509 (40.5%) and 307/486 (63.2%), respectively (OR: 0.641; 95% CI: 0.565-0.726). The average time from ovarian stimulation to pregnancy and live birth was significantly shorter in the long agonist group compared to the PPOS group (p<0.01) In Kaplan-Meier analysis, the cumulative incidence of ongoing pregnancy leading to live birth was significantly higher in the long agonist compared in the PPOS group(Log rank test, p<0.001). Cox regression analysis revealed stimulation protocol adopted was strongly associated with the cumulative live birth rate after adjusting other confounding factors (OR =1.917 (1.152-3.190), p=0.012) .Conclusion: Progestin primed ovarian stimulation was associated with a lower cumulative live birth rates and a longer time to pregnancy / live birth than the long agonist protocol in women with a normal ovarian reserve.

A Premature Rise of Luteinizing Hormone Is Associated With a Reduced Cumulative Live Birth Rate in Patients ≥37 Years Old Undergoing GnRH Antagonist In Vitro Fertilization Cycles

This is a retrospective cohort study included 1021 patients underwent a flexible GnRH antagonist IVF protocol from January 2017 to December 2017 to explore the effect of a premature rise in luteinizing hormone (LH) level on the cumulative live birth rate. All patients included received the first ovarian stimulation and finished a follow-up for 3 years. A premature rise in LH was defined as an LH level &gt;10 IU/L or &gt;50% rise from baseline during ovarian stimulation. The cumulative live birth rate was calculated as the number of women who achieved a live birth divided by the total number of women who had either delivered a baby or had used up all their embryos received from the first stimulated cycle. In the advanced patients (≥37 years), the cumulative live birth rate was reduced in patients with a premature rise of LH (β: 0.20; 95% CI: 0.05–0.88; p=0.03), compared to patients (≥37 years) without the premature LH rise. The incidence of premature LH rise is associated with decreased rates of cumulative live birth rate in patients of advanced age (≥37 years) and aggravated the reduced potential of embryos produced by the advanced age, not the number of embryos.

Effect of Female and Male Body Mass index on Cumulative Live Birth Rates in the Freeze-all Strategy

Context The impact of parental overweight/obese on cumulative live birth rate in IVF/ICSI using a freeze-all strategy is still unknown. Objective To explore the effect of parental BMI on CLBR in a freeze-all strategy over 1.5 years. Design A retrospective study. Setting Tertiary-care academic medical center Patients or Other Participants 23482 patients (35289 FET cycles) were divided into four groups according to Asian BMI classification. Intervention(s) None. Main Outcome Measure(s) CLBR. Results Female overweight/obesity had the lower tendency in CLBR (groups1-4: optimistic: 69.4%, 67.9%, 62.3%, and 65.7%; conservative: 62.9%, 61.1%, 55.4%, and 57.6%) and the prolonged time (groups 1-4: 11.0, 12.2, 15.9, and 13.8 months for 60% CLBR in optimistic method; 8.7, 9.5, 11.7, 11.0 months for 50% CLBR in conservative method). The same trend with less extent was also observed in male BMI groups. When combining parental BMI, “parental overweight/obesity” had lower CLBR and longer time for reaching CLBR&gt;50% (optimistic: 4.5 months for 60% CLBR; conservative: 3 months for 50% CLBR), the next was “only female high BMI” (optimistic: 2.1 months for 60% CLBR; conservative: 1.7 months for 50% CLBR), while “only male high BMI” couldn’t influence these. Conclusions Our results firstly showed that the priorities of parental BMI, female BMI and male BMI on affecting the 1.5-year CLBR in freeze-all strategy, and the postponed time to reach up the certain CLBR (60% in optimistic, 50% in conservative) for overweight and obese patients was only several months, not so uncertain and long as losing weight.

Ovarian Endometrioma Negatively Impacts Oocyte Quality and Quantity But Not Pregnancy Outcomes in Women Undergoing IVF/ICSI Treatment: A Retrospective Cohort Study

PurposeTo determine the impact of ovarian endometrioma per se on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes.MethodsThis retrospective study was conducted using two groups. The endometrioma group consisted of 862 women with infertility who had ovarian endometriomas and underwent their first ovarian stimulation for IVF/ICSI treatment between January 2011 to December 2019 at a public university hospital. A non-endometrioma comparison group, comprising 862 women with other infertility factors, was matched according to maternal age, body mass index (BMI), and infertility duration. Ovarian reserve and response and IVF/ICSI and pregnancy outcomes between the two groups were analyzed. Multivariate logistic regression (MLR) analysis was conducted on the basis of clinical covariates assessed for their association with live birth.ResultsThe results showed that significantly lower antral follicle count (AFC), anti-Müllerian hormone (AMH), ovarian sensitivity index (OSI), oocyte maturation and fertilization rates, blastocyst rate, number of oocytes retrieved, and available embryos were found in women with endometrioma compared with the control, respectively (P &lt; 0.05). The cumulative live birth rate per patient in women with endometrioma was lower than that of women without endometrioma (39.32% vs. 46.87%, P = 0.002). In women with endometrioma, those who underwent surgical intervention prior to IVF/ICSI treatment had higher maturation (86.03% vs. 83.42%, P = 0.003), fertilization (78.16% vs. 74.93%, P = 0.004), and top-quality embryo rates (42.94% vs. 39.93%, P = 0.097) but had fewer oocytes retrieved (8.01 ± 5.70 vs. 9.12 ± 6.69, P = 0.013) than women without surgery. However, live birth rates were comparable between women with endometrioma and women in the control group, regardless of whether they had a prior history of ovarian surgery. MLR analysis showed no correlation between endometrioma per se and live birth after being adjusted for number of top-quality embryos transferred and stage of embryo transfer.ConclusionsThe data from this study supported the conclusion that ovarian endometrioma negatively impacts oocyte quality and quantity, but not overall pregnancy outcomes, in women undergoing IVF/ICSI treatment. Endometrioma lowers the cumulative live birth rate by decreasing the number of embryos. Surgical excision of endometrioma prior to IVF/ICSI can partly improve oocyte maturation and fertilization rates but not pregnancy outcomes.

Biphasic (5–2%) oxygen concentration strategy significantly improves the usable blastocyst and cumulative live birth rates in in vitro fertilization

Oxygen (O2) concentration is approximately 5% in the fallopian tube and 2% in the uterus in humans. A “back to nature” approach could increase in vitro fertilization (IVF) outcomes. This hypothesis was tested in this monocentric observational retrospective study that included 120 couples who underwent two IVF cycles between 2014 and 2019. Embryos were cultured at 5% from day 0 (D0) to D5/6 (monophasic O2 concentration strategy) in the first IVF cycle, and at 5% O2 from D0 to D3 and 2% O2 from D3 to D5/6 (biphasic O2 concentration strategy) in the second IVF cycle. The total and usable blastocyst rates (44.4% vs. 54.8%, p = 0.049 and 21.8% vs. 32.8%, p = 0.002, respectively) and the cumulative live birth rate (17.9% vs. 44.1%, p = 0.027) were significantly higher with the biphasic (5%-2%) O2 concentration strategy. Whole transcriptome analysis of blastocysts donated for research identified 707 RNAs that were differentially expressed in function of the O2 strategy (fold-change > 2, p value < 0.05). These genes are mainly involved in embryo development, DNA repair, embryonic stem cell pluripotency, and implantation potential. The biphasic (5–2%) O2 concentration strategy for preimplantation embryo culture could increase the “take home baby rate”, thus improving IVF cost-effectiveness and infertility management.