No abstract

Objective: To investigate the characteristics and outcomes of low prognosis patients defined by POSEIDON criteria undergoing IVF treatment. Design: Retrospective cohort analysis. Setting: An IVF clinic in a public hospital. Patients: 18,455 fresh aspirated IVF cycles with subsequently frozen embryo transfer from Jan 2014 to Jan 2017 in a single IVF clinic were included in the analysis. The low prognosis patients were categorized into 4 groups based on POSEIDON criteria: group 1: age < 35, antral follicle count (AFC) ≥ 5, number of oocytes retrieved ≤ 9 in the previous cycle; group 2: age ≥ 35, AFC≥5, number of oocytes retrieved ≤ 9 in the previous cycle; group 3: age < 35, AFC < 5; group 4: age ≥ 35, AFC < 5. The non-low prognosis patients: group 5: AFC ≥ 5, previous number of oocytes retrieved > 9 oocytes; group 6: AFC ≥ 5, no previous ovarian stimulation. Intervention(s): None. Main Outcome Measure: The primary outcome was cumulative live birth rate (CLBR). Result(s): Taking group 1 as reference, the CLBR from young women in group 3 (35.5%, OR 0.9, 95% CI 0.7–1.2) was slightly lower than that in group 1 (44.6%, p = 0.615). The CLBR in group 2 (24.5%, OR 0.6, 95% CI 0.4–0.8, p = 0.004) and group 4 (12.7%, OR 0.4, 95% CI 0.3–0.6, p < 0.001) was significant lower than that in group 1. In non-poor prognosis patients, the CLBR from young women in group 5 (53.5% OR 1.3 95% CI 0.9, 1.7, p = 0.111) was a slight higher than the reference group 1 while the highest CLBR was originated from the first IVF patients with good ovarian reserve in group 6 (66.9%, OR 2.0, 95% CI 1.6, 2.4). Conclusion(s): The CLBRs and implantation rates in the young women (group 3) with diminished ovarian reserve was similar in those young women (group 1), and was significantly higher than in advanced age women with a fair ovarian reserve (group 2). Though patients in group 2 had better ovarian reserve, more oocytes and more embryos, the pregnancy outcome was inferior to that of group 3 patients with poorer ovarian reserve, fewer oocytes and fewer embryos.

Whether hepatitis B virus (HBV) infection impairs human infertility is unclear. The present retrospective case-controlled study investigated the impact of HBV on sperm parameters, ovarian stimulation, and outcomes of in vitro fertilization (IVF) and embryo transfer. A total of 224 couples with at least one partner being HBsAg-seropositive undergoing their first IVF and embryo transfer cycle were identified, which included 77 couples with female partners being HBsAg-seropositive, 136 couples with male partners being HBsAg-seropositive, and 11 couples with both partners being HBsAg-seropositive. A total of 448 both HBsAg-seronegative couples served as controls. The percentage of normal sperm morphology was significantly lower in HBsAg-seropositive male partners than that in HBsAg-seronegative male partners (11.9 ± 9.4% vs. 19.0 ± 11.9%, P < 0.01). The duration of infertility was significantly prolonged in HBV-seropositive patients compared with HBV-seronegative patients (4.9 vs. 4.1 years, P < 0.01). Couples with female partners being HBsAg-seropositive had significantly lower top-quality embryo rate than control group (22.4% vs. 31.6%, P < 0.01). In addition, the fertilization rates in groups with male or female partners being HBsAg-seropositive were both significantly lower than the matched controls (80.2% vs. 82.8%, P < 0.05; 76.6% vs. 84.3%, P < 0.01, respectively). HBV infection was also found to be associated negatively with fertilization rate by logistic regression analysis (odds ratios: 0.410, 95% confidence interval: 0.186-0.906, P < 0.05). However, there was no significant difference in clinical pregnancy rates between HBsAg-seropositive and HBsAg-seronegative group. These results suggest that chronic HBV infection is likely to represent a significant cause of infertility.

Background To determine whether gonadotropin-releasing hormone (GnRH) agonist downregulation combined with hormone replacement therapy (HRT) can improve the reproductive outcomes in frozen–thawed embryo transfer cycles for older patients (aged 36–43 years) with idiopathic recurrent implantation failure (RIF). Methods This retrospective cohort study involved 549 older patients undergoing their third cleavage-stage embryo or blastocyst transfer over a 5-year period (January 2015–December 2020) at Northwest Women’s and Children’s Hospital after in vitro fertilization/intracytoplasmic sperm injection cycles. Patients with known endometriosis or adenomyosis were excluded from the study. The patients were divided into three groups according to the endometrial preparation protocol: the natural cycle (NC) group (n = 65), the HRT group (n = 194), and the GnRH agonist downregulation combined with HRT cycle (GnRH agonist–HRT) group (n = 290). The primary outcome was the live birth rate, and the secondary outcomes were the clinical pregnancy, miscarriage, and ongoing pregnancy rates. Results The live birth rate in the GnRH agonist–HRT group (36.55%) was higher than that in the HRT group (22.16%) and NC group (16.92%) (P < 0.0001). Similarly, a logistic regression model adjusting for potential confounders showed that the live birth rate was higher in the GnRH agonist–HRT group than in the HRT group (odds ratio, 0.594; 95% confidence interval, 0.381–0.926; P = 0.021) and NC group (odds ratio, 0.380; 95% confidence interval, 0.181–0.796; P = 0.010). Conclusions The GnRH agonist–HRT protocol improves the live birth rate in frozen–thawed embryo transfer cycles for patients of advanced reproductive age with RIF. We hypothesize that the GnRH agonist–HRT protocol enhances implantation-related factors and promotes optimal endometrial receptivity, leading to an improved live birth rate. These findings are also useful for further investigating the underlying mechanism of the GnRH agonist–HRT protocol in improving the reproductive outcomes for patients of advanced reproductive age with RIF. Trial registration This research protocol was approved by the hospital institutional ethics committee (No. 2021002).

Objective: To investigate ovarian sensitivity in subgroups of patients with a low prognosis, as defined by the POSEIDON criteria, undergoing in vitro fertilization treatment and measures to improve ovarian sensitivity in these patients. Design: We conducted a retrospective cohort analysis. Setting: The study was conducted at an IVF clinic in a public hospital. Patients: A total of 32,128 fresh IVF cycles from January 2014 to October 2018 at a single IVF clinic were included in the analysis. Patients with a low prognosis were categorized into four groups based on the POSEIDON criteria. Interventions: None. Main Outcome Measure: The primary outcome measures were the follicular output rate (FORT) and the follicle-to-oocyte index (FOI). Results: The FORTs in the order from the highest to the lowest were 1.18 in group 3, 0.98 in group 4, 0.76 in group 1, and 0.68 in group 2. The trend in the FOI values was consistent with that in the FORTs. Among patients with poor ovarian sensitivity, 58.41% of patients with FORTs ≥ 0.30 in the second cycle underwent an adjustment to the ovarian stimulation (OS) protocol and 41.59% underwent an adjustment to the gonadotropin (Gn) starting dose. Among patients with normal ovarian sensitivity, 43.56% of those with FORTs ≥ 0.80 in the second cycle underwent an adjustment to the OS protocol and 56.44% underwent an adjustment to the Gn starting dose. Conclusion: Ovarian sensitivity was the highest in group 3 (young women with poor ovarian reserve), followed by groups 4 (women at advanced age with poor ovarian reserve) and 1 (young women with good ovarian reserve), and it was the lowest in group 2 (women at advanced age with good ovarian reserve). For patients with poor ovarian sensitivity, it is preferred to recommend an adjustment to the OS protocol, while for those with normal ovarian sensitivity, adjusting the Gn starting dose is preferred.

The aim of this study was to evaluate the safety of laser-assisted hatching (LAH) by comparing obstetric and neonatal outcomes between assisted hatching and control groups in cryopreserved embryo transfer cycles. A retrospective cohort analysis was carried out. A total of 699 women with 392 infants delivered were included. Laser- assisted hatching was carried out on D-3 thawed and warmed embryos before transfer in 480 cryopreserved embryos transfer cycles. Obstetric outcomes, neonatal outcomes, and congenital birth defects were recorded. A total of 815 cryopreserved embryo transfer cycles (480 in LAH group and 335 in control group) in 699 patients were analysed. Statistically significantly higher implantation (31.85% versus 16.95%), clinical pregnancy (53.96% versus 33.43%) and live delivery (44.58% versus 23.88%) rates were observed in the LAH group (all P < 0.001). For either singleton or multiple gestations, no statistically significant differences were found in mean gestational age, mean birth weight and mean Apgar score. Four major malformations occurred in the assisted hatching group and three malformations (one major and two minor) in the control group. This study did not identify any harmful effect of LAH on neonates, which suggested that LAH may be a safe treatment in cryopreserved embryo transfer cycles.

Objective: To investigate the cumulative live birth rates (CLBR) according to body mass index (BMI) in women undergoing their first in vitro fertilization (IVF). Design: Retrospective cohort analysis. Setting: An IVF clinic in a public hospital. Patients: This is a retrospective study of 14,782 patients undergoing their first fresh IVF cycles and subsequent frozen embryo transfers in our clinic from January 2014 to January 2017. The follow-up for CLBR continued until January 2019. Patients with a BMI <18.5 kg/m 2 were considered to be underweight and those with a BMI > 24 kg/m 2 were considered to be overweight. Patients with a BMI ≥ 28 kg/m 2 were considered to be obese. Intervention(s): None. Primary Outcome Measure: The primary outcome was cumulative live birth rate (CLBR). Result(s): This study illustrated the "inverted U shape" associations between body weight and IVF outcome (CLBR). The turning points in threshold analysis, as found by an automatic search, were BMIs of 18.5 and 30.4 kg/m 2. The main finding of this retrospective data analysis is that the CLBR increased in underweight women, plateaued for normal weight and overweight women with a BMI between 18.5 and 30.4 kg/m 2 , and decreased in obese women. Conclusion(s): The data suggested an "inverted U shape" association between BMI and CLBR. The CLBR increases in underweight women, plateaus in normal weight and overweight women, and then decreases in obese women.

STUDY QUESTION Does an increased dosing of FSH improve the live birth rate as compared to standard FSH dosing in expected poor responders who undergo IVF? SUMMARY ANSWER In this trial, women with an expected poor response allocated to increased FSH dosing did not have a statistically significant increase in cumulative live births as compared to a standard FSH dose. WHAT IS KNOWN ALREADY Poor ovarian reserve leads to worse IVF outcomes owing to the low number and quality of oocytes. Clinicians often individualize the FSH dose using ovarian reserve tests, including antral follicle count (AFC), and basal plasma FSH or anti-Müllerian hormone level. However, the evidence that increased FSH dosing improves fertility outcomes in women with an expected poor response is lacking. STUDY DESIGN, SIZE, DURATION We performed a parallel, open-label randomized controlled trial between March 2019 and October 2021 in an assisted reproduction centre. PARTICIPANTS/MATERIALS, SETTING, METHODS Women &lt;43 years of age with AFC &lt;10 referred for their first IVF cycle were randomized for increased or standard FSH dosing. In participants allocated to increased FSH dosing, women with AFC 1–6 started with 300 IU/day, while women with AFC 7–9 started with 225 IU/day. In participants allocated to the standard care, women started with 150 IU/day. The primary outcome was cumulative live birth attributable to the first IVF cycle including fresh and subsequent frozen-thawed cycles within 18 months of randomization. Live birth was defined as the delivery of one or more living infants ≥24 weeks’ gestation. This trial was powered to detect an 11% difference in live birth attributable to the first IVF cycle. Outcomes were evaluated from an intention-to-treat perspective. MAIN RESULTS AND THE ROLE OF CHANCE We randomized 661 women to start FSH at increased dosing (n = 328) or standard dosing (n = 333). The primary outcome cumulative live birth occurred in 162/328 (49.4%) women in the increased group versus 141/333 (42.3%) women in the standard group [risk ratio (RR) 1.17 (95% CI, 0.99–1.38), risk difference 0.07 (95% CI, −0.005, 0.15), P = 0.070]. The live birth rate after the first embryo transfer in the increased versus standard group was 125/328 (38.1%) versus 117/333 (35.1%), respectively [RR 1.08 (95% CI, 0.83–1.33), P = 0.428]. Cumulative clinical pregnancy rates were 59.1% versus 57.1% [RR 1.04 (95% CI, 0.91–1.18), P = 0.586] with miscarriage rates of 9.8% versus 14.4% [RR 0.68 (95% CI, 0.44–1.03), P = 0.069] in the increased versus standard group, respectively. Other secondary outcomes, including biochemical pregnancy, ongoing pregnancy, multiple pregnancy and ectopic pregnancy, were not significantly different between the two groups both from the first and cumulative embryo transfer. LIMITATIONS, REASONS FOR CAUTION As this study is open-label, potential selective cancelling and small dose adjustments could have influenced the results. WIDER IMPLICATIONS OF THE FINDINGS In women with predicted poor response, we did not find evidence that increased FSH dosing improves live birth rates. A standard dose of 150 IU/day is recommended at the start of IVF in these women to reduce potential adverse effects and costs. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the General Projects of Social Development in Shaanxi Province (No. 2022SF-565). B.W.M. is supported by NHMRC (GNT1176437). B.W.M. reports personal fees from ObsEva, and funding from Merck and Ferring outside the submitted work. TRIAL REGISTRATION NUMBER Registered at Chinese clinical trial registry (www.chictr.org.cn). Registration number ChiCTR1900021944. TRIAL REGISTRATION DATE 17 March 2019 DATE OF FIRST PATIENT’S ENROLMENT 20 March 2019