Total Gonadotropin Research Articles

Correlation of Recombinant FSH Doses with Follicular and Serum Level Resolvin E1 in Polycystic Ovarian Syndrome Women Undergoing ICSI

Background: Reproduction is a intricately structured process achieved by interaction of the higher centers in the brain, the gonads, and different body parts; Whereas infertility is a multifactorial pathological condition affecting approximately 10–15% of couples, especially in industrialized region.RESOLVIN E1 is a member of specialized pro resolving mediator family of bio active lipids. It has anti-inflammatory effects in various inflammatory diseases. A promising researches in their way to prove its positive role in reproduction through direct effect on folliculogenesis. It has a fundamental role in regulating follicular growth and maturation at central and peripheral levels highlighting its possible role in diagnosing and treating infertility problems. High level of RESOLVIN E1 which might play critical role in poly cystic ovarian syndrome due to its anti-inflammatory effects. Objectives: To investigate the correlation of serum and follicular RESOLVIN E1 to gonadotropin (recombinant FSH doses) in PCOS patient undergoing ICSI. Subject, Patients, Materials, and Method: A prospective cross-sectional study conducted in the high institute for infertility diagnosis and assisted reproductive technology /Al Nahrain University /Baghdad /Iraq, from November 2023 till March 2024. Twenty-nine infertile PCOS women who were undergoing intracytoplasmic sperm injection were enrolled in the study. Serum and follicular RESOLVIN E1 at day of oocyte pickup were measured using ELISA technique. Results: The current study shows significantly lower gonadotropins stimulation dose needed for PCOS females (p <0.001). It also revealed no significant correlations between total gonadotropins dose with both serum and follicular fluids resolvin E1, while there were insignificant negative correlations between serum and follicular fluids resolvin E1 with patients’ ages and body mass indices among PCOS females. Conclusions: There is no correlation between the serum and follicular RvE1 levels in PCOS infertile females.

Vaginal Progesterone Gel versus Intramuscular Progesterone for Luteal Phase Support in Suboptimal Responders Undergoing Assisted Reproductive Cycles

Background: The purpose of this research is to compare the efficacy of 8% micronized vaginal progesterone gel (VAG) at 180 mg daily versus intramuscular progesterone (IMP) in oil at 100 mg daily for luteal phase support (LPS) after fresh single embryo transfer (SET) in Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) Group 1b patients, and to ascertain whether the type of LPS predicts live birth in these patients. Methods: A total of 2420 assisted reproductive technology (ART) cycles performed in Ondokuz Mayıs University IVF Unit were analysed retrospectively. The data of POSEIDON Group 1b (unexpected suboptimal responders) who underwent antagonist in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were included. All patients were categorized into groups according to the form of LPS, specifically VAG and IMP. Pregnancy, clinical pregnancy rate (CPR), live birth rate (LBR), spontaneous abortion rate and predictors of live birth (age, infertility duration, body mass index (BMI), type of progesterone used for luteal support, serum day 3 estradiol, serum progesterone on the day of human coryonic gonadotrophin (HCG), total duration of induction, serum estradiol on the day of HCG, the total number of oocytes retrieved, number of mature oocytes obtained, average gonadotropin dose per day, total gonadotropin dose administered and total number of embryos retrieved) were analyzed. Results: There was no statistically significant difference between the micronized VAG and IMP groups in terms of age (31 (23–35) vs. 27 (23–35), p = 0.319). There were no statistically significant differences in pregnancy outcomes between the two groups concerning CPR per transfer (70.6% vs. 75.6%; p = 0.364), ongoing pregnancy per cycle (36.2% vs. 39.5%; p = 0.577), and LBR per cycle (34.4% vs. 36.1%; p = 0.785). The spontaneous abortion rates (36.2% vs. 36.8%; p = 0.921) were similar between VAG and IMP groups. The type of LPS did not emerge as a parameter predicting pregnancy (odds ratio (OR): 0.718, 95% confidence interval (95% CI): 0.652–1.313, p = 0.451), clinical pregnancy (OR: 0.598, 95% CI: 0.592–1.289, p = 0.562) and live birth (OR: 0.802, 95% CI: 0.661–1.202, p = 0.580). The logistic regression analysis aimed at assessing the influence of confounding factors, namely age, BMI, and duration of infertility on pregnancy rate, CPR and LBR, did not reveal statistically significant results (p > 0.05). Conclusions: VAG 180 mg daily provide similar pregnancy outcomes compared to 100 mg daily IMP in POSEIDON Group 1b patients undergoing antagonist fresh IVF/ICSI cycles.

Total gonadotropin dose did not affect euploid blastocyst rates: an analysis of more than 19,000 oocytes.

To evaluate whether increasing total gonadotropin (Gn) dose is associated with changes in euploid blastocyst rate in preimplantation genetic testing (PGT) oocytes. This retrospective cohort study was conducted between 2017 and 2022, and 19,246 oocytes were grouped and analyzed based on tri-sectional quantiles of total Gn doses. Single reproductive medical center. All the patients who underwent PGT cycles, including PGT for aneuploidy, monogenic disorders, and structural rearrangements, were included. Next-generation sequencing platforms for chromosomal analysis. Blastocyst formation and euploid blastocyst rates. In total, 19,246 oocytes and 5375 PGT blastocysts were analyzed. There were significant differences in blastocyst formation and euploid blastocyst rates among the groups classified according to tri-sectional quantiles of total Gn doses. Significant differences in age, body mass index (BMI), proportion of primary infertility, anti-Müllerian hormone (AMH) levels, number of oocytes retrieved, controlled ovarian stimulation (COS) regimen, type of Gn, and PGT category were observed among the three groups. After stratifying the analysis by age, BMI, infertility diagnosis, AMH levels, number of oocytes retrieved, PGT category, type of Gn, and COS regimen, significant differences were only seen in a small number of specific subgroups. Furthermore, the results of the multiple logistic regression analysis showed that the blastocyst formation and euploid blastocyst rates did not significantly increase or decrease with the total Gn dose, whether treated as a continuous variable or divided into three Gn groups as categorical variables. Notably, advancing age was a risk factor for blastocyst formation and euploid blastocyst rates. PGT for structural rearrangements was a risk factor for blastocyst formation and euploid blastocyst rates as compared with PGT for aneuploidy. In the total PGT cycles, advancing age, and preimplantation genetic testing for structural rearrangements negatively affected blastocyst formation and euploid blastocyst rates; however, the total Gn dose did not affect blastocyst formation and euploid blastocyst rates.

Analytical Investigation of the Profile of Human Chorionic Gonadotropin in Highly Purified Human Menopausal Gonadotrophin Preparations.

Highly purified human menopausal gonadotropin (HP-hMG [Menopur®, Ferring Pharmaceuticals, Saint-Prex, Switzerland]) contains a 1:1 ratio of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This analysis aimed to assess gonadotropin (FSH, LH and hCG) abundance in HP-hMG and clarify the source of hCG by assessing the presence of sulfated glycans, which are diagnostic for pituitary hCG forms due to their distinct glycosylation patterns. Additionally, the purity of each sample, their specific components, and their oxidation levels were assessed. HP-hMG samples (three of Menopur® and two of Menogon® Ferring Pharmaceuticals, Saint-Prex, Switzerland) were included in the current analyses. Brevactid® (urinary hCG; Ferring Pharmaceuticals, Saint-Prex, Switzerland) and Ovidrel® (recombinant hCG; Merck KGaA, Darmstadt, Germany) were used as control samples. Glycopeptide mapping and analysis of impurities were carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oxidation was assessed through reducing peptide mapping using LC-MS/MS. The FSH and LH in the HP-hMG samples showed sulfated glycans, while no signals of sulfated glycopeptides were detected on any site of the beta subunit of hCG. HP-hMG test samples presented the same hCG glycan distribution as the control sample (placental hCG, Brevactid®) extracted from the urine of pregnant women, suggesting a non-pituitary source of hCG. Protein impurities were estimated to constitute approximately 20-30% of the entire HP-hMG protein content in the test samples. More than 200 non-gonadotropin proteins were identified in the HP-hMG test samples, of which several were involved in embryonic development or pregnancy. The alpha subunit of the tested samples was strongly oxidized, with a relative abundance of 20% of the total gonadotropin content. Without taking into account all the protein impurities, the beta subunit of LH was detected only in traces (0.9-1.2%) in all tested HP-HMG samples, confirming the data obtained by intact molecule analysis, while high levels of beta hCG (18-47%) were observed. Advanced molecular analysis of HP-hMG indicates a primarily placental origin of hCG, as evidenced by the absence of hCG sulfated glycans and the predominance of placental non-sulfated hCG in LH activity. The analysis revealed 20-30% of protein impurities and a significant presence of oxidized forms in the HP-hMG samples. These findings are critical for understanding the quality, safety, and clinical profile of HP-hMG.

Pregnancy outcomes after superovulation-intrauterine insemination (SO-IUI) using gonadotropins versus letrozole in the obese population.

To compare fertilityoutcomes of obese patients (body mass index [BMI] ≥ 30kg/m2) undergoing superovulation and intrauterine insemination (SO-IUI) using gonadotropins versus letrozole. A single centre retrospective cohort study of obese patients undergoing SO-IUI using gonadotropins or letrozole between January/2019 and June/2022. Primary outcome was clinical pregnancy rate (intrauterine pregnancy with positive fetal heart rate). Secondary outcomes included rates of multifollicular development, multiple pregnancy, spontaneous abortion and cycle cancellation. Subgroup analysis was done stratifying by obesity class. A multivariate logistic regression model was used for primary/secondary outcomes, adjusting for clinically determined covariates. Out of 802 total identified SO-IUI cycles, 715 cycles were completed (518-gonadotropins and 197-letrozole cycles). The clinical pregnancy rates were not significantly different in obese patients undergoing SO-IUI with gonadotropins versus letrozole when adjusted for age, gravidity, parity, cause of infertility, IUI cycle number, endometrial thickness, sperm source and post-wash motile sperm count (adjusted odds ratio [aOR] 1.37, 95% confidence interval [CI] 0.72-2.59). Similarly, no significant associations were found in spontaneous abortion (aOR1.46, 95%CI 0.42-5.08), multiple pregnancy (aOR1.33, 95%CI 0.20-8.88) or cancellation rates (OR0.89, 95%CI 0.55-1.45) between the two groups. The rates of multifollicular development were also comparablebetweenthe two groups (aOR0.51, 95% CI 0.19-1.38). For cycles involving gonadotropins, higher BMI classes required higher total gonadotropin dose (p < 0.001). After adjusting for patient and cycle factors, gonadotropins and letrozole led to comparable odds of achieving pregnancy in obese patients undergoing SO-IUI. Future research in the obese population will help to better understand how to optimize fertility treatments for this growing population.

Risk factors for empty follicle syndrome in diminished ovarian reserve patients undergoing intracytoplasmic sperm injection cycles: A retrospective observational analysis.

The aim of this study is to evaluate the risk factors for empty follicle syndrome (EFS) in patients with diminished ovarian reserve (DOR) undergoing an intracytoplasmic sperm injection cycle. In this retrospective study, patients with DOR were divided into 2 groups according to the presence of empty follicles on the day of oocyte retrieval. Patient age, body mass index (BMI), anti-Müllerian hormone (AMH), baseline follicle stimulating hormone (FSH) and estradiol (E2) levels, basal antral follicle count (AFC), total gonadotropin dose, and day of stimulation were recorded as risk factors. The association between EFS and these variables was assessed using the logistic regression method and ROC curve analysis. Increased BMI, low AMH, higher baseline FSH, low baseline AFC, higher gonadotropin dose, and longer day of ovulation induction were independent risk factors for EFS in patients with DOR. ROC curve analysis showed that BMI, AMH, baseline FSH, baseline AFC, higher gonadotropin dose, and longer ovulation induction days were predictive parameters in this group. According to the current study, higher BMI, lower AMH, higher baseline FSH, lower baseline AFC, higher gonadotropin dose and longer ovulation induction days were independent risk factors for EFS in patients with reduced ovarian reserve.

Effects of obesity on clinical outcomes in diminished ovarian reserve patients undergoing intracytoplasmic sperm injection cycles.

The aim of this study is to evaluate the effects of obesity on clinical outcomes in diminished ovarian reserve (DOR) patients undergoing intracytoplasmic sperm injection cycles. In this retrospective observational cross-sectional study, women admitted to current clinic with DOR undergoing intracytoplasmic sperm injection were divided into 2 groups according to the obesity. Patient age, body mass index, anti-mullerian hormone, baseline follicle stimulating hormone and baseline estradiol levels, antral follicle count, total gonadotropin dose, day of stimulation, number of mature (MII) oocytes, and clinical pregnancy were evaluated. There were no statistically significant differences between groups in terms of age, anti-mullerian hormone, baseline follicle stimulating hormone, baseline estradiol levels, antral follicle count, and clinical pregnancy (P > .05). Total gonadotropin dose, the days of ovarian stimulation were higher and number of MII oocyte were less in the obese group (P < .05). Logistic regression analyses also revealed that the days of ovarian stimulation and number of MII oocyte were significant factors in the study group. ROC curve analysis showed obesity is a negatively affecting factor in DOR patients. Obesity causes more gonadotropin dose longer days of stimulation, and less number of MII oocyte. However clinical pregnancy rate is not negatively affected by obesity according to the current study.

P-656 Comparative clinical outcome following individualized follitropin delta dosing in Japanese women undergoing progestin-primed ovarian stimulation for in vitro fertilization /intracytoplasmic sperm injection

Abstract Study question Is ovarian stimulation with follitropin delta (FD) in its individualized regimen as efficacious as follitropin alfa and human menopausal gonadotropin (FAHMG)? Summary answer Ovarian stimulation with individualized FD dosing resulted in a significantly higher fertilization rate and number of blastocysts with good quality compared to conventional FAHMG dosing. What is known already Previous randomized controlled trials conducted in Japan, China, Europe, and both North and South America have demonstrated that ovarian stimulation using the individualized FD dosing regimen, which is based on serum anti-Müllerian hormone (AMH) levels and body weight, effectively modulated the ovarian response without compromising pregnancy and live birth rates. Study design, size, duration A retrospective study was conducted by reviewing the medical records of 1,720 IVF/ICSI cycles in 1,272 Japanese patients. The primary endpoint of the study was the ongoing pregnancy rate, assessed at 8 weeks of gestation, in the frozen-thawed embryo transfer. Participants/materials, setting, methods The FD treatment consisted of a fixed daily dose individualized according to each patient’s initial AMH level and body weight (AMH &amp;lt;2.04 ng/ml: 12 μg; AMH ≥2.04 ng/ml: 0.19 to 0.10 μg/kg; min-max 6–12 μg). The FAHMG dose was determined by the antral follicle count (AFC), with the following protocol: for AFC &amp;lt;25, 300 IU/day; for 40&amp;gt; AFC ≥25, 225 IU/day; and for AFC ≥40: 150 IU/day). A progestin-primed ovarian stimulation (PPOS) protocol was applied. Main results and the role of chance Multiple regression analyses (MRA) showed that the use of FD was negatively correlated with the number of oocytes retrieved (NOR) (P = 0.001), and positively correlated with the fertilization rate (FR) (P = 0.02). NOR was comparable between FD and FAHMG (10.9 ± 6.4 versus 11.8 ± 7.8) when the Mann-Whitney test (MW) was applied (P = 0.111), but significantly higher in FAHMG when the patient is younger than 40 years old with AMH ≥2 ng/ml (P &amp;lt; 0.01). The total gonadotropin use was significantly (P &amp;lt; 0.001) reduced from an average of 167.1 ± 46.9 μg (2789.9 ± 782.9 IU) FAHMG to 102.6 ± 31.6 μg FD. FR was significantly higher in FD compared with FAHMG (78.7% versus 74.1%, P &amp;lt; 0.05) on MW. Additionally, MW indicated a significantly higher number of good-quality blastocysts in FD (2.9±2.6) versus with FAHMG (2.4±2.5) (P &amp;lt; 0.05). The blastocysts obtained from FD also showed a significantly higher implantation rate (50.1% versus 39.7%, P &amp;lt; 0.01) and a comparable ongoing pregnancy rate (28.7% versus 25.7%, P = 0.292) compared to those from FAHMG as determined by chi-square test. The higher implantation rate in FD may be attributed to the greater number of good-quality blastocysts obtained compared with FAHMG. Limitations, reasons for caution This study only covered the clinical outcome of women undergoing PPOS protocol with frozen-thawed blastocyst transfers. Wider implications of the findings The present study shows that FD in its individualized fixed-dose regimen has the potential to improve the success rate in frozen-thawed embryo transfer across all ages and with a lower gonadotropin consumption compared to conventional FAHMG dosing. Trial registration number not applicable

O-148 Does presence of endometriosis adversely affect oocyte morphology? Evaluation of a large number of oocytes obtained from endometriosis patients, 27204 oocytes

Abstract Study question Does presence of endometriosis adversely affect oocyte morphology? Evaluation of a large number of oocytes obtained from endometriosis patients, 27204 oocytes Summary answer In the presence of endometriosis, oocyte morphology is not impaired. The rate of reaching blastocyst and fertiilization rate, also pregnancy outcomes are not affected negatively. What is known already Although there are hypothesis, theories that altered steroidogenesis and folliculogenesis, higher oxidative stress, reactive oxygen species, altered cell cycle progression, inflammation and angiogenesis in the follicular environment exposes oocytes to a hostile inflammatory environment and alters oocyte quality. There has been much debate and conflicting evidence as to whether the poorer IVF outcomes in women with endometriosis is related to altered oocyte quality. There is some evidence to suggest that impaired oocyte morphology in women with endometriosis may have an adverse impact on fertilization rate, however, most studies have shown that there is no difference in pregnancy outcomes following IVF. Study design, size, duration This retrospective, single center study evaluated 29130 ART cycles from August 2011 to March 2023,based on data obtained from Istanbul Memorial Hospital,ART and Reproductive Genetics Center.Study group included endometriosis patients(n = 4602 cycles, 27204 oocytes) and control group included non-endometriosis patients(n = 24528 cycles, 178774 oocytes).We analyzed demographic and cycle characteristics, oocyte morphology in ART cycles between the two groups.Futhermore, we compared pregnancy outcomes in frozen-thawed embryo transfer(FET) cycles (total number:11116 FET cycles; endometriosis group:2255 cycles,non-endometriosis group:8861 cycles). Participants/materials, setting, methods Patients diagnosed with endometrioma by ultrasound, diagnosed with endometriosis by laparoscopy or patients who underwent endometrioma surgery or adenomyosis detected on ultrasound were included in the study (endometriosis) group. In the control group, the patients without endometriosis were included. Mann Whitney U test and Pearson Chi-square test used. Cliff's Delta effect size (????) for non-parametric tests and Phi effect size (p) for categorical data were reported. Main results and the role of chance The sample was very large, so the statistical results were given in terms of effect size, not only p value calculated. Female age was similar. Female body mass index, number of previous cycles, duration of infertility, AMH, total gonadotropin dosage used, duration of ovarian stimulation, estradiol level on trigger day, number of aspirated oocytes, mature and fertilized oocytes, maturation and fertilization rate, rate of blastulation, rate of usable blastocyst (top and good quality), number of embryos transferred, blastocyst stage embryo transfer cycles were statistically different between the two groups (p &amp;lt; 0.001). However when the effect size examined, all variables were found to have a negligible association by Cliff's Delta or Phi effect size calculations. Oocytes obtained from endometriosis patients had statistically significantly higher severe central granulation, large perivitellin space, thick zona, polar body defect abnormalities compared to non-endometriosis patients (p &amp;lt; 0.001), Phi effect size showed negligible association for all variables. In endometriosis group compared to non endometriosis group; biochemical pregnancy (68.9% vs 72.2%, p:0.002, Phi:0.030), clinical pregnancy (61.5% vs 64.5%, p:0.007, Phi:0.025), total pregnancy loss (22% vs 24.4%, p:0.05, Phi:0.022) were statistically higher, but Phi effect sizes were negligible. Live birth were similar (52.5% vs 53.2 P:0.56) between the two groups. Limitations, reasons for caution The principal limitation of the study is retrospective design of the analysis. But the strength of the study is that included 27204 oocytes from endometriosis patients. Wider implications of the findings To our knowledge, this study includes the largest case group that investigates the endometriosis and oocyte morphology. The results show that endometriosis does not have a negative impact on oocyte morphology. Additionally, it has been shown that the presence of endometriosis does not have a negative effect on pregnancy outcomes. Trial registration number *

P-683 Progestins vs flexible GnRH antagonist for LH suppression during controlled ovarian stimulation in POSEIDON groups 3 and 4 patients: Analysis of effectiveness and cycle outcomes

Abstract Study question How do cycle outcomes differ between controlled ovarian stimulations using progestins vs flexible GnRH antagonists for LH suppression in women with diminished ovarian reserve (DOR)? Summary answer While progestin use is associated with significantly higher blastocyst rate than GnRH antagonists in POSEIDON group 4, the latter gives better results in group 3. What is known already Controlled ovarian stimulation (COS) in patients with DOR carries the additional risk of premature luteinizing hormone (LH) surge and ovulation.GnRH antagonists are popular for LH suppression in COS because of their convenient, quicker onset of action, flexibility to use GnRH agonist as a trigger and continue as double stimulation, allowing rapid pooling of embryos. Ease of oral administration, combined with cost-effectiveness and retention of all the benefits of GnRH antagonists makes progestins an attractive alternative to GnRH antagonists for COS in patients with DOR who often need multiple stimulation cycles to enable the pooling of embryos. Study design, size, duration An open-label, multicentric, randomized controlled study was conducted over 1 year from January 2023 to December 2023. 140 women aged 21- 42 years and with AMH &amp;lt;1.2 ng/dl were randomized into 2 groups in a 1:1 ratio, using either oral progestins or GnRH antagonists for LH suppression. The two groups were further comparative analyzed under POSEIDON 3 and 4 subgroups. Those with BMI &amp;gt;40kg/m2 and with partners having severely compromised semen parameters were excluded. Participants/materials, setting, methods In Group A (PPOS): Medroxyprogesterone acetate 10 mg orally was given daily with gonadotropins (hMG 300- 375 IU) from cycle day 2 until trigger. In Group B (Antagonist), patients had daily GnRH antagonist, cetrotide 0.25 mg, subcutaneous administration started when the dominant follicles reached 12-14 mm size during controlled ovarian stimulation. This was continued until the trigger. Following oocyte retrieval and ICSI, embryos were cultured until D5 and vitrified fortransfer in subsequent HRT cycles. Main results and the role of chance Patients in Group A, using PPOS, were noted to have significantly better fertilization rates than those in Group B, using flexible GnRH antagonists (0.82 + 0.2 vs 0.66 + 0.4, p-value &amp;lt;0.01). Though the number of top-quality embryos (TQE) frozen was not significantly different between groups A and B (p-value = 0.44), a significant difference in the outcome was noted when comparatively analyzed under the subgroups of POSEIDON groups 3 and 4. While patients in POSEIDON group 4 got significantly more top-quality embryos (TQE) when progestins were used for LH suppression (1 + 0.11 vs 0.77 + 0.41, p-value &amp;lt;0.01), those in POSEIDON group 3 got significantly more top-quality embryos when GnRH antagonist was used (0.94 vs 2, p-value &amp;lt;0.01). Patients in Group A and B were found to have no significant difference in the following outcomes: incidence of premature LH surge (4.3% vs 7.1%, p value= 0.71), number of days of stimulation (10.26 + 2.18 vs 10.26 +2.94, p value= 0.99), total gonadotropin dosage used (3448.64+ 1007.98 vs 3087.41 + 1260.56, p value=0.06), total number of oocytes retrieved (5.84 + 3.3 vs 4.9 + 3.4, p value=0.09) and total cycle cancellation rate (30.1% vs 35.7%, p value= 0.11). Limitations, reasons for caution The small sample size of the cases limits the current statistical power of the study. The results being encouraging need to be confirmed in a larger patient population and followed for a longer duration to enable calculation of implantation and clinical pregnancy rates for all patients. Wider implications of the findings Oral progestins are an effective and cheaper, patient-friendly alternative to injectable GnRH antagonists during COS in women with DOR. Considering the significantly higher TQEs formed, PPOS can be preferred in older, POSEIDON group 4 patients, whereas flexible GnRH antagonist protocol can be our choice in the younger, POSEIDON group 3. Trial registration number Not applicable

P-690 Medroxyprogesterone acetate versus cetrotide in oocyte donation: Non-randomized clinical trial

Abstract Study question Is oral medroxiprogesterone acetate non-inferior compared to cetrotide with respect to the number of mature oocytes retrieved at ovum pick-up in oocyte donation (OD) cycles? Summary answer MPA is comparable to cetrotide in terms of number of mature oocytes (MII) retrieved at ovum pick-up (OPU) in oocyte donation cycles. What is known already Progesterone primed ovarian stimulation (PPOS) uses progestin as an alternative to a GnRH analog for suppressing a premature LH surge during the follicular phase. Published reports indicate that both the number of MII retrieved and pregnancy rates from these oocytes are comparable to protocols using GnRH analogues. Among new stimulation approaches to OD, the use of MPA taken orally has been used successfully, avoiding the need for injecting a GnRH analogue, allowing for more comfortable and cost-effective ovarian stimulation. Another advantage is that vitrification is avoided because the woman undergoing stimulation is not the recipient of the transfer. Study design, size, duration A prospective, non-randomized clinical trial including 23 oocyte donors was performed between February 2020 and February 2021 to evaluate the non-inferiority of MPA (10 mg/day) versus cetrotide (0.25 mg/day) from day 6, in ovarian stimulation cycles triggered with triptorelin acetate. Trigger criterion was ≥6 follicles with a diameter &amp;gt;18 mm Participants/materials, setting, methods All oocyte donors who came for the first time were included. Two OS were performed, the first with a fixed antagonist protocol (hMG and cetrotide), the second PPOS (hMG and MPA). Transvaginal ultrasound was performed, and serum estradiol levels were recorded during monitoring. The main outcome was the number of MII retrieved at OPU. Secondary outcomes were embryological laboratory outcomes and reproductive outcomes in recipients. Main results and the role of chance Basic characteristics, such as age and BMI were comparable, less than 12 months between one donation and another. Duration of stimulation was similar in both OS (10 days), as well as the total gonadotropin dose up to trigger (2544 IU in MPA and 2630 IU in cetrotide). The number of MII retrieved was no different: 11.9 (SD 2.9) with MPA and 10.9 (SD 3.8) in cetrotide (p = 0.5). Recipients and embryo transfer (ET) characteristics were also similar between groups. The mean number of MII assigned to each recipient was 9.2 (SD 2.8) in MPA and 8.2 (SD 3.09) in cetrotide (P = 0.58). MII were fertilized with partner sperm in 93% cycles overall and fertilization rate was 70% in MPA versus 69% in cetrotide (P = 0.61). The number of D5 blastocysts was 4 (SD 2.9) in MPA and 3.56 (SD 2.6) in cetrotide. Overall, there was 99% of double ET and 1% of single ET, with 93.2% of ETs were performed in D5. No significant difference was found in the clinical pregnancy rate 55.3% versus 54.5% (P = 0.785); ongoing pregnancy rate 55.3% versus 50.9% (P = 0.419) and live birth rate 51.1%versus 45.5%, (P = 0.255). Limitations, reasons for caution The patients and physician were not blinded to the study. Further, a large proportion of patients were still pregnant at the end of the clinical trial, therefore live birth rates were not observed in the follow-up period. Wider implications of the findings Ovarian stimulation using MPA for LH surge prevention produces a comparable number of MII oocytes, fertilization rates and live birth rate compared to cetrotide in oocyte donation cycles with the advantage of being a more comfortable and cost-effective ovarian stimulation. Trial registration number Not applicable

P-361 Preserving fertility prior to hematopoietic stem cell transplant in post-pubertal women with sickle cell anaemia

Abstract Study question Can fertility preservation (FP) in women with sickle cell anemia (SCA) be linked to an increased risk of hematopoietic complications? Summary answer Only one participant on sixteen in our series had to discontinue the ovarian stimulation due to a complication related to a painful vaso-occlusive crisis (VOC). What is known already SCA is one of the most common severe monogenic diseases worldwide. It is a multisystemic disorder characterized by anaemia, increased haemolysis, and VOC. Despite advances in management, patients remain at a high risk of significant morbidity, especially increased thromboembolic events and early death. With the introduction of hematopoietic stem cell transplantation(HSCT) for non-malignant conditions, there is now a curative treatment for this debilitating condition. The myeloablative regimens for HSCT may impact ovarian reserve; therefore consideration of FP could be recommended. There is limited data on FP in this context and the risk of hematopoietic complications such as VOC is unclear. Study design, size, duration Cohort of women with SCA consulting at our center for FP before a HSCT project between 2016 and 2023. FP modalities were oocytes vitrification after ovarian stimulation and ovarian tissue cryopreservation (partial unilateral ovariectomy under laparoscopy). A protocol for the prevention of the risk of VOC, including hydration, oxygen therapy, and warming ± transfusion exchanges and for thromboembolic events was initiated before and during FP treatment, tailored on a case-by-case basis with the referring haematologist. Participants/materials, setting, methods The data related to hematopoietic complications (including VOC and thromboembolic event) [ps1] during FP were collected. Additionally, data on the follow-up of SCA, including received and planned treatments post-FP, were collected. This encompassed information on the completed FP treatments, preventive measures for SCA complications, and the outcomes of FP. Descriptive analysis was conducted. Main results and the role of chance During the study period, sixteen women affected with SCA aged 15–37 years have consulted for FP in our center. The mean age and BMI were 28.43±6.66 years and 21.97 ±3.46 respectively. The mean AMH level and antral follicle count were 1.77±1.70 and 15.83 ±7.12 respectively. Twelve patients underwent oocytes vitrification after mulfifollicular ovarian stimulation (OS), two had ovarian tissue cryopreservation, and 1 underwent both technics. One patient, initially planning for OS, cancelled after counselling. Among the 13 women that received an OS, 18 cycles were performed in total. The mean number of OS cycles per patient was 1.38±0.73. Protocols were antagonist (n = 16) or short agonist protocols (n = 2). The mean duration of gonadotropin treatment was 9.91±1.84 days, and the mean total gonadotropin dose was 3187.5±711.8 IU. Five OS were cancelled before oocyte retrieval because of an insufficient ovarian response. The mean number of oocytes retrieved was 8.83±5.61 per cycle. The mean number of cryopreserved oocytes was 12.00±5.66. One patient had to discontinue the OS due to a complication related to a painful VOC at 3 days of stimulation. As recommended, the hydroxycarbamide treatment was temporarily suspended to perform the FP. For patients who underwent unilateral partial ovariectomy, no complications were reported. Limitations, reasons for caution The main limitation is that this study is a small, retrospective case series; however, this represents the largest series to date. Wider implications of the findings Although limited, current data suggest that FP with specific conditioning does not pose a significant risk of complications in patients with SCA who are to undergo gonadotoxic treatment for HSCT. Trial registration number NA

P-670 The impact of fixed day-one versus day-six progestin initiation on ovarian response following progestin primed ovarian stimulation

Abstract Study question Does ovarian response differ between a fixed stimulation day (SD) 1 and SD 6 progestin start in a progestin primed ovarian stimulation (PPOS) protocol? Summary answer Fixed SD 1 and SD 6 PPOS protocols showed no significant differences in terms of ovarian response to stimulation. What is known already Ovulation prior to oocyte retrieval is a potential concern during ovarian stimulation (OS). Progestins, when compared to GnRH analogues, also effectively prevent premature ovulation with the added convenience in terms of its oral administration and lower costs. For this purpose, progestins may be started immediately with OS (SD 1) or later in the cycle, usually around SD 6, when the risk for ovulation increases. While the latter approach may be associated with a lower follicle growth suppression, evidence regarding the impact of the two protocols on ovarian response is still lacking. Study design, size, duration We conducted a single center retrospective cohort study in a private fertility clinic, including 923 patients (584 in the SD1 group and 339 in the SD6 group) who underwent 1064 OS cycles (652 in the SD1 group and 412 in the SD6 group) using a PPOS protocol between January 2016 and May 2023. Among these, 394 (37.03%) were oocyte donation cycles, 341 (32.05%) were autologous IVF/ICSI cycles and 329 (30.92%) were autologous vitrification cycles. Participants/materials, setting, methods We included women under the age of 44 who performed an OS cycle following a PPOS protocol. LH peak suppression was performed with daily desogestrel 75µg started either on SD 1 or on SD 6. The number of oocytes retrieved, number of mature (MII) oocytes, follicle-to-oocyte index (FOI) and follicular output rate (FORT) were compared between the groups. Comparisons are presented as adjusted regression coefficients (β) and 95% confidence intervals (95%CI) following multivariable linear regression. Main results and the role of chance The majority of patients in the SD1 group were donors (59.66%), while in the SD6 group most patients were doing assisted reproductive techniques (ART) with autologous oocytes (98,78%). In the SD1 group, patients were older (38.93±3.81 vs. 37.93±4.00, p &amp;lt; 0.001), had a higher antral follicle count (AFC) (20.79±8.66 vs. 14.12±9.96, p &amp;lt; 0.001), underwent OS with a lower gonadotropin dose (2036.25±766.20IU vs. 2715.20±976.40IU, p &amp;lt; 0.001) and triggered mostly with GnRHa (86.44% vs. 57.50%, p &amp;lt; 0.001). Both groups presented a similar body mass index (BMI) (22.80±2.96 vs. 21.71±3.25kg/m2, p = 0.175). Bivariate analysis revealed a higher number of oocytes retrieved (19.40±12.02 vs. 10.10±8.19, p &amp;lt; 0.001), number of MII oocytes (12.05±5.97 vs. 7.42±5.91, p &amp;lt; 0.001), FORT (81.53±20.59% vs. 73.72±23.80%, p &amp;lt; 0.001) and FOI (95.49±48.78% vs. 76.31±47.60%, p &amp;lt; 0.001) in the SD1 group. No difference was found in the cancellation rates among the two groups (1.99% for SD1 vs. 3.16% for SD6, p = 0.322). Following adjustment for age, BMI, AFC, ART treatment, type of trigger and total gonadotropin dose, no difference was found regarding the number of oocytes retrieved (β=-0.62; 95%CI -2.53 to 1.30), number of MII oocytes (β=-1.66; 95%CI -3.43 to 0.10), oocyte maturation rate (β = 2.30; 95%CI -4.60 to 9.20), FOI (β=-3.29; 95%CI -13.15 to 6.57) or FORT (β=-1.78; 95%CI -5.66 to 2.10). Limitations, reasons for caution Despite attempting to mitigate confounding effects through multivariable linear regression analysis, the retrospective nature of the study and limited sample size may still be insufficient to eliminate bias. Moreover, reproductive and perinatal outcomes were not reported. Wider implications of the findings Our study suggests that both the SD1 and SD6 PPOS protocols can be employed based on patients’ and clinicians’ preference, regardless of the type of ART treatment or patient’s ovarian reserve, without impact on ovarian response to stimulation. Trial registration number not applicable

P-615 Can the use of progestin in egg donation cycles influence morphokinetic parameters of embryos when compared with GnRH antagonist during ovarian stimulation? A case-control study

Abstract Study question Are there differences in clinical and morphokinetic parameters of embryos obtained from fresh egg donation cycles using GnRH antagonist versus PPOS on same donor? Summary answer Lower number of oocytes retrieved and faster early morphokinetics parameters were observed in PPOS protocol. What is known already Controlled ovarian hyperstimulation (COH) is a crucial step in assisted reproduction treatments and the ideal protocol should be chosen according to the patient’s profile, based on literature results, intending to achieve high effectiveness. The use of PPOS in ovarian stimulation protocols is getting attention because of its safety, efficacy and proved to be patient friendly and an economical alternative to avoid premature LH surge. In the last years, morphokinetics parameters started to be considered in embryo classification and selection, as they correlate to embryo implantation potential. Here, morphokinetics parameters were compared from two different COH in donated oocyte cycles. Study design, size, duration Case-control study including cycles from 10 oocyte donors and 20 recipient patients, whose embryos formed with fresh oocytes were cultured in a time-lapse system (Embryoscope® Plus), in a single private IVF center between Jun/2020 and Oct/2022. Each donor were submitted to two cycles: first stimulation with standard GnRH antagonist (ant) short protocol (group A) and in a posterior cycle: a second stimulation with progesterone (PPOS protocol with dydrogesterone, group B). Participants/materials, setting, methods All donors used menotropin for COH (doses adjusted according to patient’s profile). Group A started GnRh ant with follicle above 14 mm. On group B, dydrogesterone 10 mg was started on the first day of COH and maintained until the day of ovulation trigger, which was performed with GnRH agonist. Clinical and morphokinetics parameters were compared. Paired t-test, t-test or Mann-Whitney were used properly, values of p &amp;lt; 0.05 were considered significant. Main results and the role of chance A total of 70 blastocysts were analyzed, 39 from group A and 31 from group B. The following morphokinetics parameters were annotated: time of PN fading (tPNf), time to two cells (t2), three cells (t3), four cells (t4), five cells (t5), eight cells (t8), time to morula (tM), time to blastulation (tB) and KIDScoreTM. Statistically significant differences were observed for tPNf: group a) 24,01 ± 3,28h versus b) 22,59 ± 2,48h, p = 0,0484, t2: a) 26,30 ± 3,24h versus b) 24,76 ± 2,27h, p = 0,0211; t3: a) 37,04 ± 4,44h versus b) 35,53 ± 2,93, p = 0,0347 and t4: a) 38,38 ± 5,15h versus b) 36,05 ± 3,32h, p = 0,0152. Clinical characteristics of the donors were also analyzed: age, body mass index (BMI), total gonadotropin dose, antral follicular count (AFC), follicle stimulating hormone (FSH), basal hormone levels, follicle count, oocyte pick-up (OPU), altered oocytes, number of germinal vesicles, metaphase I (MI) and metaphase II (MII) oocytes. Differences were observed only between two clinical aspects: patients’ age: a) 24,2 ± 3,6 versus b) 25,0 ± 3,3, p = 0,0031 and OPU: a) 23,3 ± 9,1 versus b) 18,6 ± 8,3, p = 0,004, however both variables does not seem to affect embryo formation potential. Limitations, reasons for caution The results should be interpreted with caution due to the limitations of evaluate a small dataset of donors, resulting in low number of embryos in each group of protocols for analysis. Wider implications of the findings In this case-control study, a lower number of oocytes retrieved and faster early morphokinetics times were observed in PPOS compared to antagonist protocol. The implications of these differences still need further data analyses to compare if these findings can change clinical outcomes. Trial registration number Not applicable.

P-666 Comparison of IVF outcomes in women undergoing IVF stimulation using progestin primed ovarian stimulation (PPOS) Vs GnRH antagonist (GnRH-Antag) protocol

Abstract Study question Can PPOS achieve improved patient &amp; provider satisfaction while simultaneously blocking LH-surge, maintaining similar IVF outcomes like oocyte/embryo yield/clinical pregnancy rates(CPR) when compared to GnRH-Antag? Summary answer PPOS can achieve similar IVF outcomes as compared to GnRH-Antag protocol and is a patient friendly, cost-effective choice for ovarian stimulation without affecting oocyte/embryo yield/CPR. What is known already GnRH-Antag protocol is among the most widely used methods, as it blocks LH surge &amp; significantly lowers the risk of OHSS [Lambalk CB,2017]. However, this protocol has disadvantages like frequent monitoring, dose adjustment, high therapeutic cost and multiple injections[Ata B,2015]. PPOS successfully prevents ovulation and provides comparable IVFoutcomes (oocyte yield, blastocyst/euploid embryo rates, CPR) along with patient cost savings and increased convenience across all infertility diagnoses [Annalyn M.Welp, 2023]. It should be noted that most studies are non-randomized and comprise low to moderate-quality evidence. However, the consistency of the findings across different studies from different centres provides assurance in effect estimates. Study design, size, duration A retrospective cohort study conducted at a tertiary care fertility unit. Data for 449 women aged 21 to 40 years undergoing IVF stimulation using PPOS (n = 226) and GnRH-Antag (n = 223) protocol was retrieved from the hospital’s electronic database and analysed for a period between September 2022 to October 2023. Study population consisted of women undergoing freeze-all strategy either for lowering the risk of OHSS (hyper-responders) or for embryo pooling in view of very low ovarian reserve. Participants/materials, setting, methods For both groups either rFSH/rLH/HMG were used &amp; doses were indivisualised based on patient’s age, BMI &amp; ovarian reserve. PPOS group received twice daily dose of medroxyprogesterone acetate tablet(10 mg)/dydrogesterone(10 mg) from Day2 of cycle. GnRH-Antag group received Inj.Cetrorelix acetate (0.25 mg) daily as flexible protocol. Final oocyte maturation was induced with Triptorelin(0.2mg)/Choriogonadotropin alfa(250mcg)/both, once 2-3follicles reached 18-20mm. Transvaginal oocyte pick-up was performed 35-36h later. Women in PPOS group underwent freeze-all strategy followed by Frozen-Thawed Embryo-transfer. Main results and the role of chance Normally distributed continuous variables were compared using independent t-test, and categorical variables were compared by χ2 and Fisher’s exact test, where appropriate. Patient demographics, clinical/ovarian stimulation characteristics, embryological and IVF outcomes were compared for two groups. Patient demographics {Age(p-value:0.08), BMI(p-value:0.06), duration(p-value:0.09)/type(p-value:0.76) of infertlity}, total gonadotropin dose (p-value: 0.39) and duration of ovarian stimulation (p-value: 0.81) were comparable between the two groups. Though the mean LH level on trigger day was slightly higher in PPOS group (5.53 IU/L) than GnRH-Antag group (3.24 IU/L) (p-value: 0.02), statistically significant difference was not seen in the oocyte yield (p-value: 0.18), M-II oocytes (p-value: 0.17) &amp; fertilization rate (p-value: 0.23) in the two groups. The number of Day3 (p-value: 0.65), Day5 (p-value: 0.07) &amp; Day6 (p-value: 0.08) embryos available in the two groups were also comparable. IVF outcomes in terms of positive B-HCG result (p-value: 0.68), clinical pregnancy rate (p-value: 0.61) &amp; miscarriage rate (p-value: 0.27) showed no statistically significant difference in the two groups. Thus, we conclude that PPOS can achieve similar IVF outcomes as compared to the GnRH-Antag protocol, while at the same time proving to be patient friendly by reducing the need of multiple injection pricks, injection cost and the frequency of hospital visits. Limitations, reasons for caution This is a retrospective study and hence randomized comparison was not possible. PPOS can be used only when freeze-all strategy is planned, fresh embryo-transfer cannot be considered if need arises depending upon embryo quality. IVF service providers have to depend on patient compliance for using oral progestins to block LH-surge. Wider implications of the findings Study findings suggest that PPOS is a patient friendly and equally effective and safe IVF stimulation protocol when compared to GnRH-Antagonist. More RCT will be useful for investigating different aspects of PPOS (it’s utility for women with different ovarian reserve functions, conventional versus flexible approach, optimal dose of each progestin). Trial registration number Not applicable

P-663 Comparing clinical outcomes in PGT-A cycles using donated oocytes between progesterone and GnRH-antagonist protocols

Abstract Study question Does Progesterone Primed Ovarian Stimulation (PPOS) demonstrate comparable efficiency to the GnRH-antagonist protocol in terms of laboratory/reproductive outcomes in PGT-A cycles with donated oocytes? Summary answer PPOS demonstrates efficiency in PGT-A cycles with donated oocytes, comparable to the GnRH-antagonist protocol, providing cost-effectiveness and enhanced donor comfort. What is known already The demand for TRA cycles with donated oocytes steadily rises each year. This treatment instills high hopes for success. Ongoing advancements in donor stimulation protocols prioritize safety and comfort. The shift from LH agonist to antagonist suppresses LH peaks, and recently, PPOS has joined, offering a more comfortable, cost-effective, and equally safe alternative with fewer ultrasound checks, mitigating ovarian hyperstimulation syndrome. Study design, size, duration Retrospective assessment of an oocyte donor cohort undergoing ovarian stimulation: 182 cycles with the GnRH-antagonist protocol (Group 1: G1) and 120 with PPOS (Group 2: G2), conducted between July 2017 and June 2023. Ovarian stimulation involved 225 IU/d of FSHr or FSHu, triggering with a GnRH agonist, and subsequent biopsy of evolutionarily robust embryos after extended culture. Both fresh and vitrified oocytes, inseminated with either self or donor sperm, were included. Participants/materials, setting, methods We analyzed 1188 embryos (G1: 676; G2: 512). Trophoectoderm biopsies from D5/D6 blastocysts underwent NGS using the Illumina platform (VeriSeq Illumina®, San Diego, CA, USA). Comparison included total and MII oocyte numbers, fertilization rates, viable embryos, euploid/aneuploid embryos, mosaic embryos, and clinical outcomes: biochemical pregnancy (BPR), biochemical pregnancy loss (BPLR), clinical pregnancy (CPR), early pregnancy loss (EPLR), ongoing pregnancy (OPR), and live birth (LBR) rates. Statistical analyses were carried out using R statistical software (v.4.3.1). Main results and the role of chance The mean ages of donors (25.57±4.05) and recipients (41.82±4.06) were comparable in both groups. The male partner’s age differed (G1: 40.47±7.87; G2: 42.34±7.65) (p = 0.019). Results were adjusted for confounding factors, including recipient and donor ages, oocyte and seminal origin, and male factor variables. Ovarian stimulation duration (9.26 days), total gonadotropin dose (2015.64 IU), and oocyte origin (fresh G1: 69.8 %; G2: 62.5 %; vitrified G1: 30.2 %; G2: 37.5 %) showed equivalence. Statistical significance emerged in total oocytes retrieved (G1: 17.92±7.64; G2: 20.23±7.89) (p = 0.008), mean microinjected MII (G1: 10.25±1.79; G2: 10.07±1.36) (p = 0.040) and fertilization rate (G1: 73.98 %; G2: 79.44 %) (p = 0.001). The usable embryo rate was similar (G1: 54.78 %; G2: 54.47 %). Significant differences arose in mean biopsied embryos/cycle (G1: 3.71; G2: 4.27) (p = 0.016), but not for aneuploid embryos (G1: 29.71 %; G2: 29.49 %) (p = 0,998). Biochemical pregnancy rates were significant (G1: 48.8 %, G2: 60.4 %) (p = 0.022). Other clinical parameters showed no differences, with LBR at 35.5 % in G1 and 37.8 % in G2 (p = 0.752). Limitations, reasons for caution The study is retrospective, where we addressed potential biases by incorporating confounding variables. However, to confirm our initial findings, randomized prospective studies with an appropriate sample size are essential. Wider implications of the findings In egg donation cycles, PPOS shows optimal embryonic performance resulting in a live birth rate comparable to the GnRH antagonist protocol. Additionally, it offers cost-effectiveness and enhanced comfort for donors. Trial registration number Not applicable

Benefit from luteal phase progestin primed ovarian stimulation with clomiphene citrate supplementation in young women with diminished ovarian reserve: a retrospective study.

To compare the pregnancy outcomes of luteal phase and follicular phase progestin-primed ovarian stimulation protocol with clomiphene citrate supplementation (LPPOS+CC and FPPOS+CC) in young women with diminished ovarian reserve (DOR). A total of 483 women aged ≤35 years with DOR, who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)/embryo transfer (ET) with controlled ovarian stimulation using LPPOS+CC (n=257) or FPPOS+CC (n=226) protocols during June 2018 and December 2021 at the First Affiliated Hospital of Wenzhou Medical University, were included in this retrospective study. The baseline characteristics, superovulation results, laboratory related indicators between the two groups, and the pregnancy outcomes of women who achieved at least one high-quality cleavage-stage embryo or good-morphology blastocyst were compared between the two groups. No statistically significant differences were identified between the groups with respect to age, duration of infertility, proportion of secondary infertility, previous failed cycles, body mass index, anti-Müllerian hormone, antral follicle count, basal luteinizing hormone level, basal progesterone level, number of oocytes retrieved, oocyte maturation rate, high-quality cleavage-stage embryo cycle rate, the percentage of women with profound pituitary suppression, live birth rate and preterm birth rate (all P>0.05). The LH levels on the day of trigger [4.0 (2.7, 5.3) vs. 5.1 (3.2, 7.2) IU/L], the percentage of women with LH levels of >10 IU/L on the trigger day (3.13% vs. 10.67%), and the two pronucleus (2PN) rate of ICSI oocytes (72.16% vs. 79.56%) were significantly lower in the LPPOS+CC group than those in the FPPOS+CC group (P<0.05 or P<0.01). The duration of stimulation [11 (9, 12) vs. 9 (8, 11) d], the consumption of total gonadotropin [2213 (1650, 2700) vs. 2000 (1575, 2325) IU], the progesterone levels on the day of trigger [1.3 (0.8, 2.9) vs. 0.9 (0.6, 1.2) ng/mL], the clinical pregnancy rate [61.88% vs. 46.84%], and implantation rate [42.20% vs. 31.07%] in the LPPOS+CC group were significantly higher than those in the FPPOS+CC group (all P<0.01). Compared to FPPOS+CC, the LPPOS+CC protocol appears to have better pregnancy outcomes for young women with DOR undergoing IVF/ICSI-ET.

Advancing Age May Decrease Mitochondrial Activity in Cumulus Cells.

Background: The goal of this study was to compare mitochondrial activity in cumulus cells (CCs) between young and advancing-aged women, the factors that affect mitochondrial activity, and their association with blastocyst quality. Materials and methods: This prospective study included 80 infertile women who underwent ICSI between May and October 2023. Participants were divided into two groups: older and younger than 38. The oocyte mitochondrial activity from CCs was evaluated using MitoTracker, and the mean fluorescence intensity (MFI) was also evaluated. Results: The univariate and multivariate analyses revealed a significant difference in the MFI between the woman ≥ 38 age group and the lower age group (162.68 ± 79.87 vs. 228.39 ± 121.38; p-value = 0.005; 95%CI 19.97, 111.45). The factors that affected the MFI were women ≥ 38 years of age (p-value = 0.005; 95%CI -111.45, -19.91), total gonadotropin dosages (p-value = 0.006; 95%CI -0.08, 0.01), and gonadotropin-releasing hormone agonist (GnRHa) triggering (p-value = 0.006; 95%CI 36.46, 210.06). However, only women aged ≥38 years remained statistically significant after a multivariable regression analysis (p-value = 0.014; 95%CI -121.00, -14.30). In addition, only male age (mean age ± SD = 38.26 ± 5.13) was associated with high blastocyst quality in univariate and mixed multivariate analyses (OR 0.91; 95%CI 0.56, 3.04). The chemical pregnancy rate was not significantly different between the two age groups (34.5% vs. 56.7%; p-value = 0.162; 95%CI 0.2, 1.30). Conclusion: Advancing age decreased mitochondrial activity in CCs but did not affect blastocyst quality. By contrast, male age may be a predictor of high-grade blastocyst quality.

The comparision among euploidy of preimplantation blastocysts in different controlled ovary stimulation (COH) protocols.

To compare differences in euploidy rates for blastocysts in preimplantation genetic testing for aneuploidy (PGT-A) cycles after gonadotropin-releasing hormone agonist (GnRH-a) long and short protocols, GnRH-antagonist (GnRH-ant) protocol, progestin-primed ovarian stimulation and mild stimulation protocols, and other ovary stimulation protocols. This was a retrospective cohort study from the Assisted Reproductive Medicine Department of Shanghai First Maternity and Infant Hospital. A total of 1657 PGT-A cycles with intracytoplasmic sperm injection after different controlled ovary hyperstimulation protocols were analyzed, and a total of 3154 embryos were biopsied. Differences in euploidy rate per embryo biopsied, embryo euploidy rate per oocyte retrieved and cycle cancellation rate were compared. For the PGT-A cycles, the euploidy rate per embryo biopsied was lower in the GnRH-ant protocol than in the GnRH-a long protocol (53.26 vs. 58.68%, respectively). Multiple linear regression showed that the GnRH-ant protocol was associated with a lower euploidy rate per embryo biopsied (β = -0.079, p = 0.011). The euploidy rate per embryo biopsied was not affected by total gonadotropin dosage, duration of stimulation and number of oocytes retrieved. The embryo euploidy rate per oocyte retrieved was similar in all protocols and was negatively correlated with the total number of oocytes retrieved (β = -0.003, p = 0.003). Compared with the GnRH-a long protocol, the GnRH-ant protocol was associated with a lower euploidy rate per embryo biopsied. The total gonadotropin dosage, duration of stimulation and number of oocytes retrieved did not appear to significantly influence euploidy rates.

Effects of total gonadotropin dose on embryo quality and clinical outcomes with AMH stratification in IVF cycles: a retrospective analysis of 12,588 patients

BackgroundRecent studies about the effect of gonadotropin (Gn) dose on the clinical outcomes of IVF are still controversial, and no studies have analyzed the relationship between Gn dose and embryo quality. Since AMH is a strong predictor of oocyte quality, we aim to evaluate the relationship between total Gn dose and embryo quality and clinical outcomes at different AMH levels in IVF cycles.MethodsA total of 12,588 patients were enrolled in the retrospective study. The included cycles were categorized by serum AMH levels (AMH ≤ 1 ng/ml, 1 ng/ml < AMH ≤ 3 ng/ml, 3 ng/ml < AMH ≤ 5 ng/ml, AMH > 5 ng/ml), total Gn dosage (< 1875 IU, 1875–3750 IU and ≥ 3750 IU) and female age (< 35 years and 35–42 years). The embryo quality and clinical outcomes were the measure outcomes.ResultsThe top-day3 embryos rate decreased with the increase of total Gn dose in nearly all age and AMH subgroups, but this trend was not obvious in the AMH > 5 ng/ml group and AMH ≤ 1 ng/ml group. The blastocyst formation rate and high-quality blastulation rate had a negative relationship with Gn does for women aged < 35 years in the AMH ≤ 5 ng/ml groups, except for the AMH > 5 ng/ml group (P < 0.001). However, when women were 35–42 years old, regardless of AMH levels, the blastocyst formation rate and high-quality blastulation rate decreased as Gn dose increased. Clinical outcomes (implantation rate, clinical pregnancy rate and live birth rate) decreased with the increase of Gn dose in all ages and AMH stratifications.ConclusionsThe total dose of Gn may have different effects on embryo quality at different serum AMH levels, and the negative effects of total dose of Gn on clinical outcomes may be realized by impairing both embryo quality and endometrium.