Cumulative Pregnancy Research Articles

PREGNANCIES BY ACTS OF INTERCOURSE WITH VAGINAL PH MODULATOR: RESULTS FROM THE AMPOWER STUDY

Vaginal pH modulator (VPM; Phexxi®) is a non-hormonal, woman-controlled gel for prevention of pregnancy. In the phase 3 AMPOWER trial (NCT03243305), the seven-cycle cumulative pregnancy percentage was 13.7% with typical-use and 9.99% with perfect-use as determined by the Kaplan-Meier method. The objective of this post hoc analysis was to determine the chance of becoming pregnant by act of intercourse.

Female fecundability is associated with pre-pregnancy allostatic load: Analysis of a Chinese cohort.

Allostatic load (AL) is a practical index that reflects multi-system physiological changes which occur in response to chronic psychosocial stress. This study investigated the association between female pre-pregnancy allostatic load and time to pregnancy. We enrolled 444 women who met the inclusion criteria and were attempting to achieve pregnancy. Their allostatic load scores at baseline were evaluated by nine indicators (systolic blood pressure, diastolic blood pressure, fasting plasma glucose, plasma cortisol, noradrenaline, interleukin-6, hypersensitive C-reactive protein, high density lipoprotein cholesterol and body mass index). The participants were followed up and their pregnancy outcome ascertained 1 year later; we then calculated time-to-pregnancy. Cox models were used to estimate fecundability ratios and their 95% confidence intervals (95% CI) for different allostatic load scores. The median allostatic load score was 1 with a range of 0-6. The females were divided into four groups according to allostatic load score: group A (allostatic load=0, 150/444, 33.8%), group B (allostatic load=1-2, 156/444, 35.1%), group C (allostatic load=3-4, 100/444, 22.5%) and group D (allostatic load=5-6, 38/444, 8.6%). The cumulative pregnancy rate over 12 months for the four groups (A-D) was 55.4%, 44.5%, 50.9% and 26.9%, respectively (log-rank test, p=0.042). After adjusting for potential confounding factors, group D showed a 59% reduction of fecundability compared with group A (fecundability ratio=0.41, 95% CI 0.21-0.83). Women with a higher allostatic load score may have lower fecundability. Our findings suggest that the assessment of allostatic load during pre-conception consultation would be highly prudent.

Outcomes between non-IVF and IVF treatment after laparoscopic conservative surgery of advanced endometriosis with Endometriosis Fertility Index score >3.

Surgical excision of advanced endometriosis has been demonstrated to improve women's pain symptoms and quality of life in women in randomized placebo-controlled trials, but there is no strong evidence regarding the live birth rate. The revised American Fertility Society (r-AFS) classification for endometriosis has a limited predictive ability for fertility outcomes after surgery; therefore, EFI scoring has been advised for predicting conception after endometriosis surgery. No randomized controlled trials have investigated fertility outcomes in patients with advanced endometriosis after surgery. This study aimed to determine the outcomes of in vitro fertilization (IVF) or non-IVF treatments after conservative surgery for advanced endometriosis in patients with good prognosis Endometriosis Fertility Index (EFI) scores (>3). This prospective cohort study was conducted between April 2014 and April 2019 at a tertiary research hospital. In total, 113 women with suspected preoperative advanced endometriosis were enrolled in this study. A total of 90 women with advanced endometriosis underwent laparoscopic surgery. Fourteen patients with EFI score of ≤3 and 3 of them who had bilateral tubal occlusion were also excluded. Seventy-three women were included in this study. The remaining 30 women in the non-IVF group and 32 women in the IVF group were analyzed. The main outcome measures were cumulative pregnancy rates and live birth rates in both groups. Women who underwent IVF treatment were older than women (30 ± 3.41) who had non-IVF treatment (26.5 ± 3.07) after laparoscopic surgery (P < .001). The remaining baseline characteristics of the patients in both groups were similar. Clinical pregnancy, abortion, and live birth rates were similar in both the groups after 36 months of follow-up. This study demonstrated that cumulative pregnancy and live birth rates were similar to those of non-IVF or IVF treatments after conservative surgery for advanced endometriosis, if patients had good prognosis EFI scores. Furthermore, non-IVF treatments resulted in nearly the same clinical pregnancy results as IVF treatment within 1 year after surgery.

Predicting success of intrauterine insemination using a clinically based scoring system

PurposeTo develop a predictive score for the success of intrauterine insemination (IUI) based on clinical parameters.MethodsWe performed a retrospective cohort study evaluating the homologous IUI cycles performed at a single university-based reproductive medical center between 2009 and 2017. The primary outcome measure was pregnancy, defined as positive serum human chorionic gonadotropin (hCG) 12–14 days after IUI. Predictive factors for pregnancy after IUI were identified, and a predictive score was developed using a multivariable continuation ratio model.ResultsOverall, 1437 IUI cycles in 758 couples were evaluated. We found a per cycle pregnancy rate of 10.9% and a cumulative pregnancy rate of 19.4%. In a multivariable analysis, the probability of pregnancy was negatively associated with female age ≥ 35 years (OR 0.63, 95% CI 0.41–0.97, p = 0.034), endometriosis, unilateral tubal factor, or anatomical alteration (OR 0.54, 95% CI 0.33–0.89, p = 0.016), anti-Mullerian hormone (AMH) < 1 ng/ml (OR 0.50, 95% CI 0.29–0.87, p = 0.014), and total progressive motile sperm count (TPMSC) < 5 mil (OR 0.47, 95% CI 0.19–0.72, p = 0.004). We developed a predictive clinical score ranging from 0 to 5. Following 3 cycles, couples in our cohort with a score of 5 had a cumulative probability of achieving pregnancy of nearly 45%. In contrast, couples with a score of 0 had a cumulative probability of only 5%.ConclusionIUI success rates vary widely depending on couples’ characteristics. A simple to use score could be used to estimate a couple’s chance of achieving pregnancy via IUI, facilitating individualized counseling and decision-making.

Individualised versus Standard FSH Dosing in Predicted Poor Responders Undergoing IVF: A Randomised Controlled Trial

Background: Poor responders usually lead to detrimental effects on IVF outcomes due to low oocyte number and quality which further result in low pregnancy outcomes and increased chance of cycle cancellation. Clinicians often individualise the FSH dose using ovarian reserve tests (ORT), including antral follicle count (AFC). However, it is unclear whether individualised FSH dosing improves clinical outcomes. Aim: To understand if there is a difference in live birth rates between individualised or standard FSH dosing in poor responders? Method: Between March 2019 and April 2020, we performed a single center, parallel, open-label randomised controlled trial. Women referred for their first IVF/ICSI cycle, [Formula: see text]43 years of age, AFC[Formula: see text]10 were approached. Eligible women were randomised either to individualised or standard FSH dosing. In the individualised group, women with AFC 1-6 were assigned to 300IU/day, while women with AFC 7-9 were assigned to 225IU/day. In the standard group, women were assigned 150IU/day. The primary outcome was live birth attributable to the first ART cycle within 18 months of randomization. Results: A total of 661 women were randomised, 328 to the individualised group and 333 to the standard group. The live birth rate (follow up still ongoing) was not significantly different between the two groups [49.1% (161/328) vs 42.3% (141/333), RR: 1.16 (95%CI, 0.98-1.37), P=0.082]. The cumulative ongoing pregnancy rate for individualised versus standard dosing was 53.0% (174/328) versus 47.4% (158/333), respectively [RR: 1.12 (95%CI, 0.96-1.30), p=0.150]. The multiple pregnancy rate also did not differ between individualised and standard dosing [5.49% vs 5.71%, RR: 0.96 (95%CI, 0.51-1.80), p=0.903]. Individualised dosing reduced the occurrence of poor response compared to standard dosing [31.1% vs 48.6%, RR: 0.64 (95%CI, 0.53-0.78), p[Formula: see text]0.001]. Conclusion: The individualised dosing strategy led to lower rates of poor response, but it did not result in significantly higher ongoing pregnancy rates.

Micro-TESE Outcomes for Non-Obstructive Azoospermia — The First Australian Series

Background: Micro-dissection testicular sperm extraction (micro-TESE) for non-obstructive azoospermia (NOA) was shown to achieve the best sperm retrieval rate (SRR) compared to other techniques. However, to date there is no large series of published Australian data. Aim: To study the incidence and predicting factors of successful sperm extraction in men with NOA undergoing micro-TESE in Victoria. Method: We retrospectively analyzed the clinical data of all consecutive patients with confirmed NOA who were treated between August 2014 and April 2020 in a single medical centre in Melbourne, Victoria. None were excluded. Patients underwent micro-TESE and upon a successful sperm retrieval, sperm was either frozen for fertility preservation or used fresh for ICSI. Results: During the study period, 85 men with NOA underwent micro-TESE in our centre. The overall sperm retrieval rate (SRR) was 61.2% (52/85). All patients with a history of surgically treated cryptorchidism or childhood diseases had a successful sperm retrieval. Patients with Kleinfelter syndrome had a 75% SRR. Patients with Idiopathic NOA and patients with a history of chemotherapy had a 50% and 40% SRR, respectively. Among the different types of testicular pathology, the highest SRR was found in men with complete hyalinization (100%). Hypospermatogenesis was associated with a high SRR of 93.3%, while Sertoli-cell-only histology was associated with only 46.3% SRR. The SRR has significantly increased from 33.3% in 2015-2016 to 73.6% in 2019-2020 (p=0.003). On Multivariate logistic regression analysis, baseline FSH levels &lt;20 IU and history of childhood disease or Klinefelter syndrome were significantly associated with successful sperm retrieval. The cumulative pregnancy rate was 23.7%. Conclusion: This first report from Australia indicates that micro-TESE is an effective method for the treatment of NOA with high SRR and pregnancy rate. Our results can help patient management and counseling.

Sperm DNA fragmentation negatively influences the cumulative live birth rate in the intracytoplasmic sperm injection cycles of couples with unexplained infertility.

ObjectiveThis study aimed to determine the effect of sperm DNA fragmentation (SDF) on the cumulative live birth rate (CLBR) in intracytoplasmic sperm injection (ICSI) cycles in couples with unexplained infertility.MethodsWe conducted a prospective study of 145 couples who underwent ICSI cycles for unexplained infertility. Based on the SDF rate, patients were categorized into a low SDF group (SDF ≤30%, n=97) and a high SDF group (SDF >30%, n=48). SDF was assessed using the acridine orange test on density gradient centrifugation prepared samples. The CLBR was calculated as the first live birth event per woman per egg collection over 2 years.ResultsThe high SDF group (SDF >30%) showed a significantly lower CLBR (p<0.05) and a significantly higher miscarriage rate (p<0.05) than the low SDF group (SDF ≤30%). No significant difference was observed in the implantation and cumulative pregnancy rates between the two SDF groups. The total number of embryo transfers was stratified further into fresh and frozen embryo transfers. In the fresh embryo transfers, there were significant differences in the implantation rates, clinical pregnancy rates, and live birth rates (p<0.05) between the low SDF and high SDF groups. However, in the frozen embryo transfers, there were no significant differences in clinical outcomes between the two groups. In the multivariable logistic regression analysis, SDF was a predictor of CLBR (p<0.05) when adjusted for possible confounding factors. ConclusionHigh SDF was associated with a lower CLBR and a higher miscarriage rate in the ICSI cycles of couples with unexplained infertility.

Fertility-enhancing effect of oil-based contrast agents during hysterosalpingography and the variation of this effect within a 3-year follow-up period in infertile patients.

ObjectiveThe previous study has indicated the fertility-enhancing effect of oil-based contrast agents during hysterosalpingography (HSG) in infertile patients. However, the variation of this effect with the time frame is seldom reported. The current study aimed to explore fertility improvement using oil-based contrast agents and the change of this improvement during the 3-year follow-up period in infertile patients.Materials and methodsInfertile women who underwent HSG with oil-based contrast agents (N = 500) or water-based contrast agents (N = 500) were enrolled. Spontaneous pregnancy rate and time to pregnancy were assessed at months (M)1, M2, M3, M6, M12, M24, and M36 after HSG.ResultsThe spontaneous pregnancy rate was 79% in the oil-based group and 70.2% in the water-based group. The cumulative spontaneous pregnancy rate was increased in the oil-based group when compared with the water-based group (p = 0.015). Fertility-enhancing effect of HSG was increased in the oil-based group when compared with the water-based group at all time points {M1 [odds ratio (OR)]: 1.536}; M2 (OR: 1.455); M3 (OR: 1.494); M6 (OR: 1.356); M9 (OR: 1.288); M12 (OR: 1.249); M24 (OR: 1.131); and M36 (OR: 1.125). While this superiority of the fertility-enhancing effect of HSG in the oil-based group (vs. the water-based group) was decreased with the time frame. Similar findings were also observed based on the physiological cycles.ConclusionThe HSG procedure with oil-based contrast agents shows a fertility-enhancing effect when compared to water-based contrast agents. This improvement could last at least 1 year while dropping to the normal level within the subsequent 2 years.

Reproductive outcomes of infertile couples undergoing assisted reproductive technology who are carriers of chromosomal abnormalities: a retrospective cohort study

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

Ovulation induction in anovulatory infertility is obsolete

Women with polycystic ovary syndrome make up the vast majority of patients with anovulatory infertility. The commonly accepted treatment guidelines recommend ovulation induction for timed intercourse as the first-line treatment. After a 2-year treatment period, the cumulative pregnancy rates with a singleton live-born baby reached 71% and 78% in two prospective studies. Despite aiming for monofollicular growth, multifollicular responses with subsequent multiple/higher order multiple pregnancies are a dreaded risk associated with ovarian induction. However, the lengthy treatment, the increase of maternal age and the psychological effects of ‘obligatory intercourse’ are also factors challenging the concept of ovarian induction as the first treatment approach in anovulatory infertility. Nowadays, individualized IVF treatment with cycle segmentation, freeze-all strategies and single-embryo transfers in frozen embryo transfer cycles dramatically reduces the risk of multiple pregnancies, and a cumulative pregnancy rate of 83% can be achieved over three complete cycles, thereby reducing exposure to fertility medication and time to pregnancy. Although on first sight ovarian induction might present the easier and less costly approach, efficient and individualized IVF treatments with low complication rates and the chance of preventing multiple pregnancies challenge this concept, and it seems that the time has come to abandon ovarian induction in anovulatory infertility.

A novel GnRH antagonist protocol based on LH levels versus traditional flexible GnRH antagonist protocol in PCOS patients undergoing in vitro fertilization: study protocol for a randomized controlled, non-inferiority trial

BackgroundThe gonadotropin-releasing hormone (GnRH) antagonist protocol is advantageous given that it can avoid severe ovarian hyperstimulation syndrome (OHSS), especially for patients with polycystic ovary syndrome (PCOS). Basic and clinical evidence has shown that a threshold of luteinizing hormone (LH) stimulation is required for adequate follicular development and oocyte maturation. Ultra-low or high levels of LH are detrimental to pregnancy outcomes. We previously demonstrated that LH could be an indicator for the timing and dosage of antagonist administration in a retrospective study.Methods/designIn this randomized, single-center, non-inferiority trial, we aim to test the hypothesis that there is no significant difference in cumulative ongoing pregnancy rates between PCOS patients stimulated with LH-based flexible protocol versus traditional flexible GnRH antagonist protocol. The primary efficacy endpoint will be the cumulative ongoing pregnancy rate per cycle. The secondary outcomes will be clinical pregnancy rate, cancelation rate, serious OHSS rate, and cost-efficiency. The cumulative ongoing pregnancy rate per cycle in PCOS women was 80%. Considering that a non-inferiority threshold should retain 80% of the clinical effect of a control treatment, a minimal clinical difference of 16% (two-sided: α, 2.5%; β, 20%) and a total of 196 patients were needed. Anticipating a 10% dropout rate, the total number of patients required was 216.DiscussionThe results of this study will provide evidence for the efficacy and safety of the LH-based flexible GnRH antagonist protocol in PCOS patients. Moreover, it evaluates the cost-efficiency of both protocols.Trial registrationChinese Clinical Trial Registry ChiCTR1800018129. Date assigned: 31 August 2018. Protocol version: 1.0 (18 July 2017)

Luteinizing hormone-based modified GnRH antagonist protocol in normal responders undergoing in vitro fertilization treatment: A multi-center randomized controlled trial.

ObjectiveTo study the clinical efficacy and cost-effectiveness of a modified gonadotrophin-releasing hormone (GnRH) antagonist protocol based on luteinizing hormone (LH) levels through one complete assisted reproductive technology (ART) cycle in normal responders.DesignNon-inferiority, multicenter randomized controlled trial.SettingUniversity-based hospitals and an academic medical center.PatientsA total of 372 patients fulfilled the inclusion criteria and were eligible to participate.Intervention(s)Participants were randomized at a 1:1 ratio and stimulated with the conventional flexible GnRH antagonist protocol (control group) or LH-based modified GnRH antagonist protocol (study group).Main Outcome MeasuresThe primary outcome was the cumulative ongoing pregnancy rate per aspiration. The secondary outcomes were number of oocytes retrieved, number of good quality embryos, cumulative positive βhCG rate, cumulative clinical pregnancy rate, pregnancy loss rate, moderate and severe ovarian hyperstimulation syndrome (OHSS), and financial expenditure.ResultsThe cumulative ongoing pregnancy rate was 65.1% in the study group and 70.1% in the control group (odds ratio, 0.79; 95% confidence interval, 0.50–1.26; P = 0.33). The multivariate regression analyses results showed that the number of retrieved oocytes was positively associated with the odds for a higher cumulative ongoing pregnancy rate (adjusted odds ratio, 1.11, 95% confidence interval, 1.06–1.17, P < 0.001). The treatment protocol, female age, and body mass index were not independent predictors. The incremental cost-effectiveness ratio for luteinizing hormone-based gonadotrophin releasing hormone antagonist protocol versus the conventional flexible gonadotrophin releasing hormone antagonist protocol was estimated at 3568.6 USD for each additional ongoing pregnancy.ConclusionThe luteinizing hormone-based gonadotrophin releasing hormone antagonist protocol had clinical efficacy similar to the conventional flexible gonadotrophin releasing hormone antagonist protocol in normal responders undergoing in vitro fertilization treatment but was more cost-effective considering the cumulative ongoing pregnancy rate in the entire assisted reproductive technology cycle.Clinical Trial Registration www.chictr.org.cn, identifier: ChiCTR1800018077URL of the registration site http://www.chictr.org.cn/edit.aspx?pid=27389&htm=4.Trial registration date29 August 2018.Date of first patient enrollment1 September 2018.

Does Serum LH Level Influence IVF Outcomes in Women with PCOS Undergoing GnRH-Antagonist Stimulation: A Novel Indicator.

Objective: To explore the influence of LH levels on the IVF/ICSI outcomes in women with PCOSundergoing GnRH-antagonist stimulation protocol. Methods: A total of 142 IVF/ICSI patients in which the females were diagnosed with PCOS and underwent GnRH-antagonist protocol for ovarian stimulation were enrolled. Patients were divided into three groups based on basal LH (bLH) level, LH level on trigger day (hLH), and the ratio of hLH/bLH. The LH levels detected on different days in the stimulation cycle as well as their relationships with the IVF/ICSI outcomes were investigated. The main outcomes we observed were the number of oocytes retrieved, the cumulative chemical pregnancy rate, clinical pregnancy rate, and live birth rate. Other factors included the number of normally fertilized oocytes (2PN), top-quality embryo rate, and total Gn dose. Results: There was no significant difference in the included outcomes and baseline characteristics among different groups based on bLH levels. When patients were grouped according to hLH levels (≤2 mIU/mL, 2–5 mIU/mL and ≥5 mIU/mL), we found decreased levels of basal FSH and LH in the group of hLH ≤ 2 mIU/mL than the other two groups. Then the ratio of hLH/bLH was calculated for each patient. Patients with hLH/bLH ≥ 1 had a higher top-quality embryo rate than those with hLH/bLH between 0.5 and 1.0. Nevertheless, the cumulative clinical pregnancy rate was significantly higher in the hLH/bLH ≤ 0.5 group than in the other two groups. Conclusions: The study proposed the hLH/bLH ratio as a potential in predicting the influence of LH level on the embryo development potential as well as pregnancy outcomes in women with PCOS undergoing GnRH-antagonist stimulation cycles.

Clomiphene citrate priming increases sensitivity during ovarian stimulation in poor ovarian responders undergoing in vitro fertilization treatment: a retrospective cohort study

This single-centre retrospective cohort study aimed to investigate whether a clomiphene citrate (CC) priming protocol could increase ovarian sensitivity in poor ovarian responders. It included 294 patients (374 ovarian stimulation cycles). Of these, 193 cycles were treated by a CC priming antagonist protocol (study group) and 181 by the classical flexible gonadotropin-releasing hormone antagonist protocol (control group). Stimulation data and laboratory and clinical outcomes were compared between the groups. The results showed that in the study group, total gonadotropin dosage and dosage per follicle were considerably lower, the follicle-to-oocyte index was significantly higher, and the gonadotropin duration was shorter. After adjusting for potential confounders, multivariate regression analysis showed that cumulative ongoing pregnancy remained comparable between the groups (adjusted odds ratio: 0.761, 95% confidence interval: 0.300–1.933, p = 0.566). Age, body mass index, gonadotropin dosage per follicle, and the follicle-to-oocyte index were negatively associated with the reproductive outcomes. The result of the sensitivity analysis showed that patients in the study group were administered less gonadotropin at a lower gonadotropin dosage per follicle and for a shorter duration. In conclusion, the CC priming antagonist protocol offered a convenient and patient-friendly way to increase ovarian sensitivity during ovarian stimulation in poor ovarian responders.

Impact of dyslipidemia on the cumulative pregnancy outcomes after first ovarian stimulation.

ObjectivesTo investigate the cumulative live birth rate (CLBR) according to lipid metabolism in patients with or without polycystic ovarian syndrome (PCOS) undergoing their first complete in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles.PatientsA total of 1,470 patients with PCOS and 3,232 patients without PCOS who underwent their first complete IVF/ICSI cycles from January 2016 to June 2018 were included. During a minimum of 2 years of follow-up, they had achieved at least one live birth or used all available embryos. The cumulative pregnancy outcomes were compared based on the patients’ blood lipid parameters, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), in the two populations. Patients with an abnormal level of one or more of these four indicators were considered the dyslipidemia group. Patients whose four indicators were normal were considered the control group.ResultsAmong 1,470 patients with PCOS, the cumulative pregnancy outcomes were similar in the dyslipidemia group and control group. Logistic regression analysis showed that the TC levels were significantly negatively associated with the cumulative live birth rate (CLBR) after adjustment for confounding factors such as age and BMI (aOR 0.81, 95% CI 0.66-0.98, P<0.05). Among the 3,232 patients without PCOS, there was no significant difference in the cumulative pregnancy outcomes between the dyslipidemia group and the control group. No significant correlations were found in other logistic regression analyses.ConclusionsTC negatively impacts the CLBR after first ovarian stimulation in PCOS patients. PCOS patients with dyslipidemia caused by elevated TC may have a poor CLBR.

Evaluating the efficacy of ovulation stimulation with intrauterine insemination in women with diminished ovarian reserve compared to women with normal ovarian reserve.

To assess the efficacy of ovulation induction and intrauterine insemination (IUI) in couples with diminished ovarian reserve (DOR). Women aged 20-39 years and men younger than 50 years were included. Four "ovarian reserve groups" were created according to anti-Müllerian hormone (AMH) and the partner's age. Gestational sac finding on ultrasound examination was the primary outcome measure. The study was carried out on a total of 770 cycles of 362 women in an infertility cohort that consisted of 75 women with DOR treated by 153 cycles and 287 women without DOR treated by 617 cycles. The pregnancy rate was similar in the four ovarian reserve groups in terms of first, second, third plus fourth, and total attempts of IUI cycles. Moreover, the pregnancy rate, miscarriage rate, and multiple pregnancy rate were similar. We found no difference in the cumulative pregnancy rate among the groups after four IUI cycles. Multivariate logistic regression analysis of the entire cohort revealed that infertility duration, post-wash sperm count, and follicle number greater than 11 mm on the day of human chorionic gonadotropin trigger were independent predictors of pregnancy (P< 0.001). Neither age nor AMH predicted pregnancy after ovulation stimulation and IUI. Ovulation stimulation and IUI are equally effective in women with DOR and in women with normal ovarian reserve in terms of pregnancy rate, multiple pregnancy rate, and miscarriage rate per IUI cycle or cumulative pregnancy rate after four cycles of IUI.

PGT for structural chromosomal rearrangements in 300 couples reveals specific risk factors but an interchromosomal effect is unlikely

Research questionWhat factors affect the proportion of chromosomally balanced embryos in structural rearrangement carriers? Is there any evidence for an interchromosomal effect (ICE)? DesignPreimplantation genetic testing outcomes of 300 couples (198 reciprocal, 60 Robertsonian, 31 inversion and 11 complex structural rearrangement carriers) were assessed retrospectively. Blastocysts were analysed either by array-comparative genomic hybridization or next-generation sequencing techniques. ICE was investigated using a matched control group and sophisticated statistical measurement of effect size (φ). Results300 couples underwent 443 cycles; 1835 embryos were analysed and 23.8% were diagnosed as both normal/balanced and euploid. The overall cumulative clinical pregnancy and live birth rates were 69.5% and 55.8%, respectively. Complex translocations and female age (≥35) were found to be risk factors associated with lower chance of having a transferable embryo (P < 0.001). Based on analysis of 5237 embryos, the cumulative de-novo aneuploidy rate was lower in carriers compared to controls (45.6% versus 53.4%, P < 0.001) but this was a ‘negligible’ association (φ < 0.1). A further assessment of 117,033 chromosomal pairs revealed a higher individual chromosome error rate in embryos of carriers compared to controls (5.3% versus 4.9%), which was also a ‘negligible’ association (φ < 0.1), despite a P-value of 0.007. ConclusionsThese findings suggest that rearrangement type, female age and sex of the carrier have significant impacts on the proportion of transferable embryos. Careful examination of structural rearrangement carriers and controls indicated little or no evidence for an ICE. This study helps to provide a statistical model for investigating ICE and an improved personalized reproductive genetics assessment for structural rearrangement carriers.

Existence of chronic endometritis and its influence on pregnancy outcomes in infertile women with minimal/mild endometriosis.

This study aimed to evaluate the prevalence of chronic endometritis (CE) in women with minimal/mild endometriosis and to analyze whether CE affects their pregnancy outcomes. This retrospective study included 201 infertile women who were diagnosed with minimal/mild endometriosis after undergoing hysteroscopy combined with laparoscopy from January 2016 to December 2018. Immunohistochemistry was used to detect CD138 and CD38, which are specific markers of plasma cells in the endometrial stroma to diagnose CE. Subsequently, we investigated the prevalence of CE and the effects of CE on spontaneous cumulative pregnancy rate, live birth rate, and miscarriage rate within 24 months after surgery. The prevalence of CE in infertile women with minimal/mild endometriosis was 24.38%. Patients diagnosed with CE showed a significantly lower cumulative pregnancy rate and live birth rate compared with women without CE (46.51% vs. 71.13% [P=0.004]; 44.19% vs. 63.38% [P=0.025]). However, the rate of miscarriage in women with CE was also lower than in women without CE (0 vs. 7.04%, P=0.074). Since CE had an adverse effect on cumulative pregnancy rate and live birth rate in infertile women with minimal/mild endometriosis, we suggested that diagnosis and treatment of CE may improve their pregnancy outcomes.

Pregnancy rate in IVF patients with unexpected poor response to ovarian stimulation

Objective To evaluate whether an unexpected poor response (cases with ≤3 oocytes) leads to a reduction in the pregnancy rate in IVF cycles compared to a suboptimal response (controls with 4-9 oocytes) in women with adequate ovarian reserve. Methods A nested case-control study performed in a retrospective cohort of couples undergoing IVF at the Infertility Unit of the ASST Lariana. Cases and controls had adequate ovarian reserve and were matched 1:1 for female age and number of previous cycles. Cumulative clinical pregnancy rate per oocyte retrieval was the main outcome. Results Overall, 113 cases and 113 matched controls were included; the median number of available oocytes was 2 and 6, respectively. The cumulative pregnancy rate per cycle was significantly reduced in cases compared to controls with a crude odds ratio = 0.45 [95% Confidence Interval: 0.28-0.82]. A binomial logistic model indicated that an increase in one oocyte increases the odds for cumulative pregnancy rate per cycle by 1.27 in women with 9 oocytes or less. The cumulative pregnancy rates per cycle in cases and controls, according to female age were respectively: 29% versus 54% in patients aged <35 years (p = 0.036); 22% versus 43% in patients aged 36-39 years (p = 0.048) and 11% versus 13% in patients 40-45 years old (p = 0.72). Patients belonging to older age groups showed decreasing probability of cumulative clinical pregnancy rates both among cases and controls group (p < 0.05). Conclusions The number of available oocytes significantly affects the probability of success in IVF cycles with unexpected impaired ovarian response.

O-291 Cumulative pregnancy rates of two strategies: day 3 fresh embryo transfer followed by day 3 or day 5 frozen embryo transfer, a Randomized Controlled Trial

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