In Vitro Fertilization/intracytoplasmic Sperm Injection Research Articles

Embryo transfer on day 5 or day 6 blastocysts versus blastocysts quality in programs for frozen blastocysts

The aim of the present study was to analyze the high-quality blastocyst (HB) rate in all embryo frozen cycles and investigate the pregnancy outcomes for day 5/day 6 (D5/D6) blastocysts with respect to the blastocyst quality in programmed single vitrified-warmed blastocyst transfer (SVBT). We performed a retrospective study comparing D5/D6 HBs in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) for all blastocyst frozen cycles. Patients were below 37 years at the oocyte collection in their first fresh cycle without fresh transfer. A total of 195 IVF/ICSI cycles and 670 blastocysts were analyzed. The IVF HB rate was higher than that of ICSI (52.7% vs. 42.6%; P<0.05). The D5 HB rate was much higher than the D6 HB rate (61.6% vs. 29.4%; P<0.05). There were 21% (40/195) of cycles that only had D6 blastocysts, of which IVF cycles were lower than ICSI (19.8% vs. 28.5%; P<0.05). The clinical pregnancy rate and implantation rate in the D5 group were significantly higher than the rates in the D6 group (57.4% vs. 46.2%, 58.9% vs. 47.3%; P<0.05). However, the clinical pregnancy rate and implantation rate of the D5 HBs were not significantly different from those of the D6 HBs (60% vs. 54.5%, 62% vs. 56.3%; P>0.05).

Associations between maternal MTHFR polymorphisms and embryological outcomes in Korean patients with infertility undergoing IVF/ICSI cycles

Objective Methylenetetrahydrofolatereductase (MTHFR) is important for folate metabolism, which is involved in DNA synthesis and cell growth. However, the relationship between Maternal MTHFR polymorphisms and outcomes in assisted reproduction remains controversial. This is the first study to explore the effect of MTHFR polymorphisms on the embryological outcomes in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles in Korean patients with infertility. Materials and methods This retrospective cohort study included 173 women who underwent MTHFR genotyping between July, 2021 and June, 2022. The embryologic outcomes of 301 IVF/ICSI cycles were compared between groups according to MTHFR polymorphisms using ANOVA and Chi-square test. Results Oocyte maturation rates were 80.0%, 75.0%, and 71.4% for MTHFR 677CC, 677CT, and 677TT, respectively. Cleaved embryo formation and transplantable embryo rates were comparable across various maternal MTHFR 677 genotypes. Good-quality embryo (GQE) rate was higher for MTHFR 677CT than those for 677CC and 677TT (40.0% vs. 29.4%, p = 0.001 and 40.0% vs. 33.3%, p = 0.025, respectively). When analyzing the combined MTHFR genotypes, the oocyte maturation rate was significantly lower in 677TT than in 677CC 1298AA/677CC 1298AC and 677CC 1298CC/677CT 1298AA/677CT 1298AC (71.4% vs. 76.7%, p = 0.012 and 71.4% vs. 75.7%, p = 0.029, respectively). The MTHFR 677CC/1298CC, 677CT/1298AA, and 677CT/1298AC genotypes had the highest GQE rates. Conclusions MTHFR 677TT genotype, which had the lowest enzymatic activity, had the lowest oocyte maturation rate. The combined MTHFR 677CC/1298CC, 677CT/1298AA, and 677CT/1298AC genotypes with intermediate enzyme activities had higher GQE rates. However, no differences were observed in the transplantable embryo rate between MTHFR genotypes.

Growth Hormone Pretreatment in Poseidon Type IV Undergoing ICSI Using Minimal Induction Protocol: A Randomized Controlled Trial

Abstract The aim of this of this clinical trial is to explore whether growth hormone (GH) pretreatment is beneficial for patients with poor ovarian reserve undertaking invitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. Poor ovarian reserve patients with anti-Mullerian hormone (AMH) <1.2 ng/mL were recruited and divided into the GH adjuvant group (GH+ group) and the counterpart without GH pretreatment (GH- group). One-to-one case-control matching was performed to adjust essential confounding factors between the GH+ group and GH- group. A total of 132 patients were included in the present study with 66 patients in each group. minimal ovarian stimulation protocols were applied for ART treatment. Patients were recruited according to POSEIDON group 4 (PG4, age ≥35 years). The demographic data, cycle characteristics, and clinical outcomes between the GH+ group and GH- group, as well as in the further stratified analysis of PG4 were compared. GH adjuvant showed no significant effect on the ovarian response and live birth rate in poor ovarian reserve patients. GH adjuvant failed to promote the live birth rate in PG4. In conclusion, GH pretreatment has no significant difference as an adjuvant in POSEIDON poor ovarian reserve patients older than 35.

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

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

New Insight of Lipiodol Flush on Pregnancy Outcomes in Women with Recurrent Implantation Failure Undergoing IVF/ICSI: a Prospective Study Based on Propensity Score Matching.

Pregnancy outcomes in women with recurrent implantation failure (RIF) undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI): does treatment with lipiodol flush matter? In this propensity score-matched study, we recruited 966 RIF patients who underwent IVF/ICSI from two tertiary hospitals. These patients were divided into groups based on whether they received lipiodol flush or not. Further stratification was applied to investigate the effect of lipiodol flush on pregnancy outcomes in RIF patients with different cycle type of embryo transferred. Then, patients subjected to lipiodol flush were categorized into three groups based on the duration of the interval: short interval (≤ 3months), moderate interval (3-6months), and long interval (≥ 6months). The groups were well-matched at baseline. The lipiodol flush group exhibited a significantly lower incidence of biochemical pregnancy (46.27% vs. 56.22%, p = 0.046) and live birth (25.87% vs. 37.31%, p = 0.014). Subgroup analysis for fresh embryo transfer cycles revealed no significant differences in pregnancy outcomes. Among RIF patients underwent frozen-thawed embryo transfer cycle, a statistically significant difference in the live birth rate was observed in the lipiodol flush group when compared to the control group (26.40% vs. 37.21%, p = 0.030). Analysis of different lipiodol flush intervals demonstrated a significantly lower live birth rate in the lipiodol flush group. Our results challenge the value of lipiodol use in clinical practice for the treatment of RIF.Trial registration: Chinese Clinical Trial Registry, ChiCTR1900024273. Registered 4 July 2019.

Rescue ICSI Improved Cumulative Live Birth Rate for Cycles with Second Polar Body Extrusion Rate

ObjectiveTo determine the indications for early rescue intracytoplasmic sperm injection (ICSI) application. DesignA retrospective cohort study SubjectsThe study included 19,808 patients who underwent conventional in vitro fertilization (IVF) or rescue ICSI for their first cycles between February 2017 and December 2021. ExposureRescue ICSI cycles constituted the study group, where oocytes that had not extruded the second polar body 4-6 hours after insemination were rescued by ICSI. The control group consisted of conventional IVF cycles with no interventions to rescue oocytes without the second polar body. Generalized additive models (GAMs) were constructed to describe the relationship between the second polar body extrusion rate and cumulative live birth rate in conventional IVF and rescue ICSI cycles, respectively. The cutoff value of the second polar body extrusion rate guiding rescue ICSI application was determined from the intersection point of GAMs. Maternal age range applicable to rescue ICSI was further analyzed using the same method. Clinical outcomes were compared between conventional IVF and rescue ICSI cycles across different second polar body extrusion rate and maternal age subgroups. Main outcome measuresThe second polar body extrusion rate and maternal age range for rescue ICSI application, normal fertilization rate, and cumulative live birth rate. ResultsGAMs showed that the cutoff value for the second polar body extrusion rate about rescue ICSI application was 50%. When the rate <50%, normal fertilization rate and cumulative live birth rate (63.7% vs. 46.1%, OR: 1.609, 95% CI: 1.276-2.030) were significantly higher in rescue ICSI cycles than conventional IVF cycles. When the rate ≥50%, rescue ICSI cycles had similar normal fertilization rate and cumulative live birth rate compared to conventional IVF cycles. Further analysis on maternal age in cycles with second polar body extrusion rate <50% released that rescue ICSI cycles showed a higher cumulative live birth rate (67.7% vs. 48.3%, OR: 1.732, 95% CI: 1.361-2.202) than conventional IVF cycles for women aged < 38 years. ConclusionIVF cycles with second polar body extrusion rate <50% in women aged < 38 years was applicable to early rescue ICSI.

Constructing a predictive model for live birth following fresh embryo transfer in antagonist protocol for polycystic ovary syndrome.

The present research aims to assess the factors that influence live birth outcomes following fresh embryo transfers using antagonist protocols in individuals diagnosed with polycystic ovary syndrome (PCOS). Furthermore, it seeks to develop a predictive nomogram model to facilitate clinical decision-making and provide personalized treatment strategies. This retrospective cohort research analyzed the clinical data of 1242 individuals having PCOS who went through fresh embryo transfers employing antagonist protocols and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at Fujian Provincial Maternal and Child Health Hospital between January 2018 and December 2022. Individuals were assigned randomly to a modeling group (869 cases) and a validation group (373 cases) in a 7:3 ratio. The Boruta algorithm and multivariable logistic regression were utilized to identify independent risk factors linked to live births after transfer. A predictive nomogram was subsequently developed. The discriminatory power of the model and its accuracy were monitored by utilizing receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. Multivariable logistic regression analysis identified several independent factors that influence live birth rates in fresh embryo transfer cycles for individuals having PCOS using antagonist protocols, including female age, body mass index (BMI), infertility duration, serum testosterone levels, progesterone levels at the time of human chorionic gonadotropin (hCG) injection, number of high-quality cleavage-stage embryos, type of embryo transferred, and the total number of embryos transferred. Based on these findings, a predictive nomogram was developed. The area under the ROC curve stood at 0.804 (95% confidence interval (CI), 0.775-0.833) for the modeling group and 0.807 (95% CI, 0.762-0.851) for the validation group. Calibration curves confirmed that the predictions of the nomogram closely matched the actual live birth outcomes. Decision curve analysis highlighted that the model provides significant net benefits for predicting live birth rates, with optimal performance across a probability range of 16.5 to 88.6%. Independent factors, including female age, infertility duration, BMI, serum testosterone levels, progesterone levels on the day of hCG injection, and the number and type of high-quality cleavage-stage embryos transferred are pivotal in influencing live birth outcomes in fresh embryo transfer cycles under antagonist protocols in individuals with PCOS undergoing IVF/ICSI treatments. The predictive nomogram developed from these factors offers substantial predictive accuracy and clinical utility, providing a reliable basis for clinical prognosis, targeted interventions, and the development of personalized treatment plans.

Analysis of assisted reproductive outcomes for gynecologic cancer survivors: a retrospective study

ObjectiveTo examine the reproductive outcomes of assisted reproductive technology (ART) in gynecologic cancer patients and to assess maternal and neonatal complications.MethodsWomen diagnosed with gynecologic cancer who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment between 2013 and 2021 at Shanghai Ji Ai Genetics and IVF Institute were included in this study. Infertile women without any history of cancer were matched to the cancer group. The primary outcome was the cumulative live birth rate. Baseline and follow-up data were compared between groups using Student’s t-tests for normally distributed variables and with Chi-square test for categorical variables. A propensity score-based patient-matching approach was adopted to ensure comparability between individuals with and without specific cancer type.ResultsA total of 136 patients with a history of gynecologic cancer and 241 healthy infertile controls were included in this study. Endometrial cancer constituted 50.70% of the cases and cervical cancer constituted 34.60% of the cases. The cancer group exhibited significantly shorter duration of stimulation, lower levels of estradiol, lower number of retrieved oocytes, day-3 embryos, and blastocysts compared to the control group (P < 0.05). The cumulative live birth rate of the gynecologic cancer group was significantly lower than that of the control group (36.10% vs. 60.50%, P < 0.001). Maternal and neonatal complications did not significantly differ between the groups (P > 0.05). The endometrial cancer and cervical cancer groups showed significantly lower cumulative live birth rates than their matched controls (38.60% vs. 64.50%, P = 0.011 and 24.20% vs. 68.60%, P < 0.001, respectively).ConclusionsThese findings highlight the decreased occurrence of pregnancy and live birth in female gynecologic cancer patients undergoing ART, particularly in endometrial cancers and cervical cancers. These findings have important implications for counseling and managing gynecologic cancer patients undergoing ART.

Efficacy analysis of letrozole combined with gonadotropin-releasing hormone antagonists in patients with high risk of ovarian hyperstimulation syndrome undergoing total embryo freezing

Objective: To investigate the clinical efficacy of letrozole combined with gonadotropin-releasing hormone antagonists (GnRH-ant) in patients at high risk of ovarian hyperstimulation syndrome (OHSS) who underwent total embryo freezing after oocyte retrieval. Methods: A retrospective analysis was conducted on 348 female patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at the Reproductive and Genetic Hospital of the First Affiliated Hospital of Zhengzhou University between January and July 2023. Due to their high risk of OHSS, these patients canceled fresh embryo transfer and opted for total embryo freezing. Based on patients' preferences, those who received GnRH-ant and letrozole after oocyte retrieval were categorized as the intervention group (164 cases), while those who did not receive these medications were categorized as the control group (184 cases). The first luteal phase after oocyte retrieval, OHSS grading, ovarian volume, and estradiol (E2) levels were evaluated in both groups. A multivariate logistic regression model was used to analyze factors related to moderate-to-severe OHSS among patients at high risk of OHSS who underwent total embryo freezing after oocyte retrieval. Results: The age of the intervention and control groups was (29.3±3.8) and (29.4±4.1) years, respectively (P=0.821). The duration of the first luteal phase post-oocyte retrieval was shorter in the intervention group [(7.16±1.39) days] compared to that in the control group [(13.88±2.11) days] (P<0.001). The incidences of mild, moderate, and severe OHSS in the intervention group were 75.0% (123 cases), 23.8% (39 cases), and 1.2% (2 cases), respectively, whereas in the control group they were 12.5% (23 cases), 60.9% (112 cases), and 26.6% (49 cases) (P<0.001). E2 levels on the 2nd and 6th days after oocyte retrieval [M(Q1,Q3)] in the intervention group were 1 520.0 (1 213.8, 1 884.8) and 108.5 (45.6, 218.0) ng/L, respectively, which were statistically significantly lower than those in the control group [1 666.0 (508.8, 1 702.0) ng/L] and [1 761.0 (826.0, 2 546.5) ng/L] (P<0.001). The abdominal cavity effusion in the intervention group [M(Q1,Q3)] were 19.5 (0, 30) and 0 mm, statistically significantly less than those in the control group [46.0 (0, 61.0) mm] and [54.5 (0, 69.5) mm] (P<0.001). On the 6th day after oocyte retrieval, the bilateral ovarian volumes in the intervention group were smaller than those in the control group (P<0.001). Multivariate logistic regression analysis indicated that no combined treatment with letrozole and GnRH-ant was a risk factor of moderate to severe OHSS. The risk of developing moderate to severe OHSS in the control group was 35.312 times higher than that in the intervention group (OR=35.312, 95%CI: 17.488-71.300). Conclusions: The administration of letrozole combined with GnRH-ant post-oocyte retrieval in patients at high risk of OHSS can prevent the occurrence of moderate-to-severe OHSS, shorten the first luteal phase, accelerate the reduction of serum E2 levels, and promote the recovery of ovarian volume and absorption of abdominal fluid.

Clinical predictors of successful outcomes for couples with nonobstructive azoospermic male partners undergoing micro-TESE.

Nonobstructive azoospermia (NOA) is the most challenging and complex clinical scenario for infertile men. Besides circumstances such as hypogonadotropic hypogonadism, surgical sperm retrieval is typically necessary, and microdissection testicular sperm extraction (micro-TESE) is the procedure of choice for men with NOA desiring to father children with their own gametes. Micro-TESE results in the highest numbers of sperm cells retrieved for use with in vitro fertilization/intracytoplasmic sperm injection (ICSI) in comparison to all other techniques for surgical sperm retrieval in men with NOA. Several factors may affect sperm retrieval rate and ICSI outcomes, including the patient's age, testicular volume, histopathological and genetic profile, and serum hormone levels. This article aims to review the medical literature describing predictors of successful micro-TESE and the outcomes of ICSI in men with NOA.

Effect of different treatment protocols on in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) outcomes in adenomyosis women: a systematic review and meta-analysis

ObjectivesPregnancy outcomes of different ovarian stimulation protocols for in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) in patients with adenomyosis are not explicit. This meta-analysis aimed to systematically evaluate the effects of...

Can We Harvest More Mature Oocytes by Repeating Gonadotropin-Releasing Hormone Agonist Doses in Polycystic Ovarian Syndrome Patients at Risk of OHSS in Antagonist Cycles? A Randomised Clinical Trial.

There is an ongoing debate about the optimal dosage of gonadotropin-releasing hormone (GnRH) agonist for oocyte triggering in polycystic ovarian syndrome (PCOS) patients at risk for ovarian hyperstimulation syndrome (OHSS). In this study, we intend to ascertain whether the use of repeated doses of a GnRH agonist for oocyte triggering in these patients can enhance the outcomes of controlled ovarian stimulation (COS) for in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. This randomised clinical trial enrolled 70 PCOS women candidates for IVF/ICSI with the standard antagonist protocol at Royan Institute (Tehran, Iran) from May 2020 to June 2022. Patients at risk of OHSS with oestradiol (E2) levels >3000 pg/ml on the day of trigger were randomly assigned to a control or experimental group. Group A (control group) patients received 0.2 mg triptorelin (Decapeptyl®) for final oocyte maturation. Group B (experimental group) patients received a second dose of 0.1 mg Decapeptyl®12 hours after their first dose, for a total dose of 0.3 mg. IVF/ICSI outcomes were compared between the groups. Ultimately, 35 women from the study group and 33 from the control group completed the treatment cycle. Both groups were comparable in terms of demographic characteristics, baseline hormonal profiles, and PCOS phenotypes. The dosage of gonadotropin, stimulation duration, number of retrieved oocytes, oocyte maturation rate, and oocyte recovery ratio did not significantly differ between the groups. No significant differences were found in terms of the number of blastocyst and cleavage embryos, nor the quality of obtained embryos between the groups. The mild to moderate OHSS rate was significantly lower in the study group (P=0.038). A second dose of GnRH agonist 12 hours after the first dose did not improve the number and maturity of oocytes, or pregnancy outcomes in PCOS patients (registration number: NCT04600986).

Psychiatric disorders among females with prolonged infertility with or without in vitro fertilization/intracytoplasmic sperm injection failure: a cross-sectional study

ObjectivesThe present study seeks to deepen understanding of the negative impacts of infertility, with a spotlight on the experiences of Egyptian women who faced prolonged periods of infertility, and emphasizing the role that faliures of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles may play in exacerbating their psychiatric disorders and impairing their sexual functions.MethodsEmbarking on a cross-sectional approach, this study was operationalized within the outpatient sectors of the Obstetrics and Gynecology Departments, synchronized with Psychiatry Departments, at Tanta University Hospitals from September 1, 2018, to December 31, 2022. The targeted population encompassed women experiencing prolonged infertility (≥ 5 years), categorically divided into two groups for meticulous analysis: Group I (with a history of IVF/ICSI failure) and Group II (without any IVF/ICSI attempts). Diagnostic tools, including the Arabic versions of the Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), and the Female Sexual Function Index (FSFI), were deployed to scrutinize the mental health and sexual function outcomes of the participants.ResultsA total of 236 women participated in this study (126 in Group I and 110 in Group II), with primary infertility prevalent in 73.31% of cases, averaging a duration of 9.28 ± 3.40 years. Our findings indicated a substantial presence of depression (58.47%), anxiety disorders (35.17%), and sexual dysfunctions (43.64%). Notably, significant differences (p < 0.0001) emerged between the groups on the HAM-D, HAM-A, and FSFI scales, with endometriosis showcasing the worst effects.ConclusionsThe findings conclusively pinpoint a pronounced link between prolonged infertility and exacerbated mental health conditions, alongside impaired sexual functions, thereby negatively affecting the quality of life of the affected women. This revelation underscores the pressing need for integrated psychiatric consultations in the therapeutic protocols of women grappling with infertility, particularly those with a history of endometriosis or failed IVF/ICSI cycles, to foster a more holistic approach to infertility management and care.

P-605 Effectiveness of follitropin delta in patients with potential poor response: A post hoc analysis from the ESTHER-1 trial

Abstract Study question What is the effectiveness of individualised follitropin delta dosing compared to conventional follitropin alfa dosing in patients with potential poor response undergoing ovarian stimulation? Summary answer Individualised follitropin delta dosing provides a favourable efficacy and safety balance and is as good as follitropin alfa in patients with potential poor ovarian response. What is known already Poor ovarian response to controlled ovarian stimulation constitutes a challenge in in-vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment. The dosing algorithm of follitropin delta incorporates the prediction of ovarian response based on anti-Müllerian hormone (AMH), an accurate marker of ovarian reserve, and body weight, for an individualised dosing. In the general IVF/ICSI population and potential high responders, individualised follitropin delta reduces the risk of ovarian hyperstimulation syndrome (OHSS) and/or preventive interventions for OHSS, with sustained efficacy compared to conventional follitropin alfa. However, the performance of follitropin delta in the subpopulation of patients with potential poor response has not been evaluated. Study design, size, duration Post hoc analysis of 332 patients with potential poor response from the ESTHER-1 trial (determined by AMH level at screening &amp;lt;9 pmol/L). Patients received the maximum daily dose of 12 µg follitropin delta (fixed dosing throughout stimulation) as stipulated by the dosing algorithm for patients with AMH &amp;lt;15 pmol/l, or follitropin alfa at a starting dose of 150 IU, with potential dose adjustments from stimulation day 6 and onwards (maximum daily dose of 450 IU). Participants/materials, setting, methods Participants were women, 18–40 years, undergoing their first IVF/ICSI cycle in a GnRH antagonist protocol, including triggering with human chorionic gonadotrophin, IVF/ICSI insemination, and single or double blastocyst transfer on Day 5. Ultrasound was performed 10–11 weeks after transfer to confirm ongoing pregnancy. All pregnancies were followed until birth. Study outcomes include number of oocytes retrieved and number of good quality blastocysts, ongoing pregnancy and live birth rates, cycle cancellation and OHSS rates. Main results and the role of chance A total of 332 patients (25.0% of the overall ESTHER-1 population) had serum AMH at screening of &amp;lt; 9 pmol/l and were included in the analysis: 168 were treated with follitropin delta and 164 were treated with follitropin alfa. Baseline characteristics were similar between the treatment groups, with a mean age of 34.8 years, a median AMH of 5.7 pmol/l and a mean weight of 64.5 kg. With follitropin delta, the mean daily dose was 12.0 µg and with follitropin alfa 12.4 µg, resulting in mean total doses of 104.6 µg and 112.3 µg, respectively. The mean number of oocytes retrieved was 5.8 ± 3.5 with follitropin delta and 5.5 ± 3.6 with follitropin alfa and the mean number of good-quality blastocysts was 1.2 ± 1.4 with both treatments. The ongoing pregnancy rate was 29.8% with follitropin delta and 29.3% with follitropin alfa and the live birth rates were 29.2% and 28.7%, respectively. Thirteen patients (7.7%) treated with follitropin delta and 14 (8.5%) treated with follitropin alfa had their cycles cancelled due to poor response. One case of OHSS (0.6%) was observed in the follitropin delta group, and 3 cases (1.8%) were observed in the follitropin alfa group. Limitations, reasons for caution The main limitation of the study is its post hoc nature. Furthermore, the study is based on a relatively small number of patients. Wider implications of the findings This subgroup analysis, alongside the normoresponder and the potential hyperresponder subgroup of the ESTHER-1 trial, adds evidence for the effectiveness of follitropin delta across all ovarian reserve subgroups of the infertile population. Trial registration number NCT01956110

O-014 Cumulative live birth associated with number of oocytes in ovarian stimulation with follitropin delta: an individual patient data meta-analysis

Abstract Study question What is the optimum number of oocytes retrieved to maximise cumulative live birth rates in the fresh and subsequent frozen cycles following follitropin delta stimulation? Summary answer The cumulative live birth rate increased steadily with number of oocytes retrieved up to a plateau starting at ∼21 oocytes retrieved. What is known already Live birth rate (LBR) per fresh ovarian stimulation cycle is the conventionally reported outcome of in vitro fertilisation (IVF). In recent years, there has been a marked increase in number and successful outcomes of cryopreserved cycles, suggesting that the cumulative live birth rate (CLBR) has emerged as a more clinically relevant outcome. In the fresh cycle, the number of oocytes retrieved is regarded as a prognostic factor for LBR. A similar association has been shown for CLBR implying that CLBR increases with the number of oocytes and continues to increase beyond the plateau observed for fresh cycle LBR. Study design, size, duration Individual patient data meta-analysis of 1746 patients from 4 randomised controlled trials using follitropin delta for ovarian stimulation. The analysis included patients with ≥1 oocyte retrieved following stimulation. The CLBR in the fresh and subsequent frozen cycles was evaluated. Predicted CLBR was obtained using a logistic regression analysis with fractional polynomials to assess the association between number of oocytes retrieved and CLBR. Subgroup analyses were performed based on age, AMH and number of oocytes retrieved. Participants/materials, setting, methods Participants were women, 18–42 years, undergoing their first or second in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) cycle in a GnRH antagonist/long agonist protocol with human chorionic gonadotrophin or GnRH agonist triggering and IVF/ICSI insemination. Single or double blastocyst transfer was performed on Day 5 and all viable surplus blastocysts were cryopreserved. All pregnancies from the fresh cycle and frozen cycles initiated within 1 year after start of stimulation were followed until birth. Main results and the role of chance The study included 1746 patients who underwent a total of 2948 cycles; 1746 fresh and 1202 frozen. In total, 740 patients (42.4%) initiated frozen cycles (maximum of 6). The study population had a mean age of 33.8 years and a median AMH level of 17.0 pmol/l. The mean number of oocytes retrieved was 12.4, the fresh cycle LBR was 29.1% and the CLBR was 51.4%. The CLBR steadily increased with number of oocytes retrieved, reaching above 60% at &amp;gt; 15 oocytes and above 70% at &amp;gt; 20 oocytes. The CLBR started to plateau at ∼21 oocytes. Subgroup analyses by number of oocytes retrieved, age group or AMH group demonstrated that the CLBR decreased with increasing age (57.1%, 51.6% and 35.8% at &amp;lt; 35, 35-37 and ≥38 years). In comparison it was similar for AMH &amp;lt;15 and ≥15 pmol/l (52.0% and 50.9%, respectively). A continued increase in CLBR from 15 oocytes retrieved was observed in older patients (≥38 years); from 41.3% to 53.4% to 58.7% at 15-19, 20-24 and ≥25 oocytes. No equivalent benefit was observed in younger patients, where corresponding rates were 72.5%, 68.0% and 78.8% in patients &amp;lt;35 years, and 70.3%, 73.1% and 71.5% in patients 35-37 years. Limitations, reasons for caution A limitation of this study is the small number of patients with &amp;gt;20 oocytes retrieved. The individual pooled studies were heterogenous regarding number of blastocysts transferred and hCG/agonist trigger. Wider implications of the findings The current individual patient data meta-analysis suggests an increase in CLBR with number of oocytes retrieved up to a plateau starting at ∼21 oocytes following ovarian stimulation cycles with follitropin delta and subsequent frozen cycles. An increase in CLBR from 20 oocytes was evident in older but not younger patients. Trial registration number NCT01956110, NCT03564509, NCT03740737, NCT03738618

P-655 Live birth rate in the fresh cycle associated with number of oocytes in ovarian stimulation with individualised follitropin delta: an individual patient data meta-analysis

Abstract Study question What is the optimum number of oocytes retrieved to achieve a live birth for women undergoing ovarian stimulation with individualised follitropin delta? Summary answer The live birth rate (LBR) in the fresh cycle was highest in the range of 8-14 oocytes retrieved, peaking at 11 oocytes. What is known already The number of oocytes retrieved following ovarian stimulation for assisted reproductive technologies is regarded a prognostic marker of pregnancy outcome, where high numbers increase chances of live birth but also the risk of complications, especially ovarian hyperstimulation syndrome (OHSS). Thus, an optimum range of oocytes retrieved is essential. Still, there is no consensus regarding this range in fresh cycles. Optimum numbers between 6 and 15 oocytes have been suggested, taking the risk of OHSS into consideration. The individualised dosing algorithm for the recombinant follicle-stimulating hormone follitropin delta has a target range of 8–14 oocytes. Study design, size, duration Individual patient data meta-analysis of 1772 patients from 5 randomised controlled trials using individualised dosing of follitropin delta for ovarian stimulation, with fixed daily dosing based on serum anti-Müllerian hormone (AMH) and body weight. The analysis included patients with ≥1 oocyte retrieved. Outcomes of LBR and OHSS in the fresh stimulation cycle were evaluated in relation to number of oocytes retrieved. Subgroup analyses were performed based on age, AMH and number of oocytes retrieved. Participants/materials, setting, methods Participants were women, 18–42 years, undergoing first or second in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) cycle in a GnRH antagonist/long agonist protocol with human chorionic gonadotrophin or GnRH agonist triggering and IVF/ICSI. Single or double embryo/blastocyst transfer was performed on Day 3/5. All pregnancies were followed until birth. Predicted live birth was obtained using a logistic regression analysis with fractional polynomials to assess the association between number of oocytes retrieved and live birth. Main results and the role of chance The studied population (n = 1772) had a mean age of 32.6 years and median AMH of 17.7 pmol/l. Mean number of oocytes retrieved was 10.4, the LBR was 32.1% and the OHSS rate (any grade and onset) was 6.6%. The LBR steadily increased with the number of oocytes retrieved up to a plateau starting at 8 oocytes, with a LBR above 34% in the range of 8-14 oocytes retrieved, peaking at 34.9% for 11 oocytes. Beyond 14 oocytes, LBR gradually declined. By number of oocytes (grouped), the LBR was 27.8%, 33.6% and 30.9% at 1-7, 8-14 and ≥15 oocytes. In patients with embryo transfer, corresponding rates were 32.8%, 37.2% and 38.7%. In the subgroup analyses, LBR decreased with increasing age (32.7%, 30.7% and 23.4% at &amp;lt; 35, 35-37 and 38-42 years) while it was similar for AMH &amp;lt;15 and ≥15 pmol/l (30.4% and 31.3%, respectively). LBR was highest at 8-14 oocytes in patients &amp;lt;35 years (28.0%, 36.2% and 32.4% at 1-7, 8-14 and ≥15 oocytes), while it was consistently low (&amp;lt;26%) in patients 38-42 years, irrespective of number of oocytes retrieved. The OHSS rate (any grade) increased from 2.1% with 1-7 oocytes, to 5.2% with 8-14 oocytes and 17.0% with ≥15 oocytes. Limitations, reasons for caution A limitation of this study is the small number of patients with &amp;gt;20 oocytes retrieved in the studied population. Wider implications of the findings The current individual patient data meta-analysis suggests an optimum range of 8-14 oocytes retrieved to achieve a live birth in fresh cycles with follitropin delta. Furthermore, the analysis demonstrates a marked increase in OHSS rate from 15 oocytes retrieved. The results support the appropriateness of individualised follitropin delta dosing regimen. Trial registration number NCT01956110, NCT03228680, NCT03296527, NCT03564509, NCT03809429

Comparison of pregnancy outcomes between 4th day morula and 5th day blastocyst after embryo transfer: a retrospective cohort study

BackgroundThis study was designed to evaluate pregnancy outcomes between morulae transferred on day 4 (D4) and blastocysts transferred on day 5 (D5).MethodsFrom September 2017 to September 2020, 1963 fresh transfer cycles underwent early follicular phase extra-long protocol for assisted conception in our fertility center were divided into D4 (324 cases) and D5 (1639 cases) groups, and the general situation and other differences of patients in both groups were compared. To compare the differences in pregnancy outcomes, the D4 and D5 groups were further divided into groups A and B based on single and double embryo transfers. Furthermore, the cohort was divided into two groups: those with live births (1116 cases) and those without (847 cases), enabling a deeper evaluation of the effects of D4 or D5 transplantation on assisted reproductive outcomes.ResultsIn single embryo transfer, there was no significant difference between groups D4A and D5A (P > 0.05). In double embryo transfer, group D4B had a lower newborn birthweight and a larger proportion of low birthweight infants (P < 0.05). The preterm delivery rate, twin delivery rate, cesarean delivery rate, and percentage of low birthweight infants were lower in the D5A group than in the D5B group (P < 0.05). Analysis of factors influencing live birth outcomes further confirmed the absence of a significant difference between D4 and D5 transplantation in achieving live birth (P > 0.05).ConclusionWhen factors such as working life and hospital holidays are being considered, D4 morula transfer may be a good alternative to D5 blastocyst transfer. Given the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) success rate and risk of twin pregnancy, D4 morula transfer requires an adapted decision between single and double embryo transfer, although a single blastocyst transfer is recommended for the D5 transfer in order to decrease the twin pregnancy rate. In addition, age, endometrial thickness and other factors need to be taken into account to personalize the IVF program and optimize pregnancy outcomes.

P-616 Impact of Dehydroepiandrosterone sulfate and Free Androgen Index on pregnancy and neonatal outcomes in PCOS patients

Abstract Study question What were the effects of free androgen, DHEAS on pregnancy and neonatal outcomes and the cut-off value of East Asian population with PCOS ? Summary answer PCOS patients with biochemical hyperandrogenism show unsatisfactory clinical PR and CLBR when undergoing assisted reproductive technology (ART). What is known already 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 different 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. Study design, size, duration 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. Participants/materials, setting, methods This retrospective cohort study included 1647 PCOS patients. The diagnosis of PCOS was based on the Rotterdam criteria.Exclusion criteria included patients with congenital adrenal hyperplasia, androgen-secreting masses, oocyte donation cycles, and PGT cycles. Main results and the role of chance Higher FAI levels (&amp;gt;6.4) were associated with decrease in clinical pregnancy rate (PR) (58.91% vs. 51.47%, p = 0.064), live birth rate (LBR) (42.42% vs. 32.35%, p = 0.011), cumulative pregnancy rate (CPR) (p = 0.032), and cumulative live birth rate (p = 0.032). When DHEAS levels exceeded 9.5 μmol/L, there was a significant decrease in clinical PR (60.33% vs. 49.55%, P = 0.008), LBR (42.73% vs. 32.73%, P = 0.012). Negative correlations were also observed between DHEAS levels and cumulative pregnancy rate (p = 0.031) and cumulative live birth rate (CLBR) (p = 0.031). Both FAI and DHEAS elevated is associated with the lowest clinical pregnancy rate (45.95%). Conversely, when solely FAI is elevated, the pregnancy rate increases to 58.10%, while an elevation in DHEAS alone is associated with a pregnancy rate of 61.44%, both of which are lower than when neither FAI nor DHEAS are elevated(62.73%). The live birth rates exhibit a similar trend(30.00%vs40.00%vs41.83%vs44.48%). 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. Limitations, reasons for caution Firstly, the data used to develop the model were obtained from a single center with a relatively small sample size. Secondly, the patients included in this study were predominantly of slim physique with a lower proportion of obesity. Wider implications of the findings Both adrenal-derived DHEAS and ovarian-derived FAI are responsible to the unfavorable pregnancy outcomes in lean PCOS women. Trial registration number 2020B1212060029

Relationship between Platelets, Plateletcrit and Lymphocytes in the Complete Blood Count and Recurrent Implantation Failure: A Retrospective Study

Background: Approximately 10% of women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment experience recurrent implantation failure (RIF). The causes for RIF are complicated. Inflammatory processes and thrombophilia play important roles in the development of RIF. This retrospective study was conducted to investigate whether there is an association between inflammatory parameters, including platelets (PLTs), plateletcrit (PCT) and lymphocytes in the complete blood count (CBC) and RIF. Methods: This was a single-center retrospective evaluation of 150 women who had a history of RIF and 163 controls who had a live birth after the first embryo transfer. Basal characteristics, CBC and coagulation parameters of both groups were compared. Results: Compared with the controls, the women with a history of RIF had significantly lower PLT, PCT and lymphocyte counts (p = 0.03, p = 0.019 and p = 0.012, respectively). Receiver operating characteristic curve analysis revealed that PLT had a sensitivity of 48.6% and a specificity of 66.4% with a cutoff value of 271.5 (area under the curve (AUC): 0.575); PCT had a sensitivity of 77% and a specificity of 38.9% with a cutoff value of 0.245 (AUC: 0.575); and lymphocyte count had a sensitivity of 49.3% and a specificity of 71% with a cutoff value of 2.015 (AUC: 0.577) for predicting RIF. The multivariant receiver operating characteristic (ROC) analysis revealed a cutoff value of 0.508 with a sensitivity of 70.3% and a specificity of 48.9% (AUC: 0.599) (p = 0.004). Conclusions: PLT, PCT and lymphocyte counts in patients with RIF are significantly reduced, although they are not effective parameters for predicting RIF.

Nomogram to predict the probability of clinical pregnancy in women with poor ovarian response undergoing in vitro fertilization/ intracytoplasmic sperm injection cycles.

Poor ovarian response (POR) is associated with decreased clinical pregnancy rates, emphasizing the need for developing clinical prediction models. Such models can improve prognostic accuracy, personalize medical interventions, and ultimately enhance live birth rates among patients with POR. This study aims to develop and validate a prognostic model for predicting clinical pregnancy outcomes in individuals with POR undergoing in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. A retrospective cohort of 969 patients with POR undergoing fresh embryo transfer cycles at the Reproductive Center of Fujian Maternal and Child Health Center from January 2018 to January 2022 was included. The cohort was randomly divided into model (n = 678) and validation (n = 291) groups in a 7:3 ratio. A single-factor analysis was performed on the model group to identify variables influencing clinical pregnancy. Optimal variables were selected using LASSO regression, and a clinical prediction model was constructed using multivariate logistic regression analysis. The model's calibration and discrimination were assessed using receiver operating characteristic (ROC) and calibration curves, while the clinical utility was evaluated using decision curve analysis. Multivariate logistic regression analysis revealed that the age of the women (odds ratio [OR] 0.936, 95% confidence interval [CI] 0.898-0.976, P = 0.002), body mass index (BMI) ≤ 24 (OR 2.748, 95% CI 1.724-4.492, P < 0.001), antral follicle count (AFC) (OR 1.232, 95% CI 1.073-1.416, P = 0.003), anti-Müllerian hormone (AMH) (OR 1.67, 95% CI 1.178-2.376, P = 0.004), number of mature oocytes (OR 1.227, 95% CI 1.075-1.403, P = 0.003), number of embryos transferred (OR 1.692, 95% CI 1.132-2.545, P = 0.011), and transfer of high-quality embryos (OR 3.452, 95% CI 1.548-8.842, P = 0.005) were independent predictors of clinical pregnancy in patients with POR. According to the receiver operating characteristic (ROC) analysis, the prediction model exhibited an area under the curve (AUC) of 0.752 (0.714, 0.789) in the model group and 0.765 (0.708, 0.821) in the validation group. The clinical decision curve demonstrated that the model held maximum clinical utility in both cohorts when the threshold probability of clinical pregnancy ranged from 6-81% to 12-82%, respectively. Clinical pregnancy outcomes in patients with POR who underwent IVF/ICSI treatment were influenced by several independent factors, including the age of the women, BMI, AFC, AMH, number of mature oocytes, number of embryos transferred, and transfer of high-quality embryos. A clinical prediction model based on these factors exhibited favorable clinical predictive and applicative value. Therefore, this model can serve as a valuable tool for clinical prognosis, intervention, and facilitating personalized medical treatment.