Gonadotropin Dose Research Articles

Combining single-cell RNA sequencing and network pharmacology to explore the target of cangfu daotan decoction in the treatment of obese polycystic ovary syndrome from an immune perspective.

Polycystic ovary syndrome (PCOS) is a heterogeneous gynecological endocrine disorder linked to immunity. Cangfu Daotan Decoction (CFDT), a classic Chinese medicine prescription, is particularly effective in treating PCOS, specifically in patients with obesity; however, its specific mechanism remains unclear. Part 1: Peripheral blood mononuclear cells were collected on egg retrieval day from obese and normal-weight patients with PCOS and healthy women undergoing in vitro fertilization (IVF)-embryo transfer. Next, scRNA-seq was performed to screen the key genes of bese patients with PCOS. Part 2: Active ingredients of CFDT and obesity-related PCOS targets were identified based on public databases, and the binding ability between the active ingredients and targets was analyzed. Part 3: This part was a monocentric, randomized controlled trial. The obese women with PCOS were randomized to CFDT (6 packets/day) or placebo, and the healthy women were included in the blank control group (43 cases per group). The clinical manifestations and laboratory outcomes among the three groups were compared. Based on the scRNA-seq data from Part 1, CYLD, ARPC3, CXCR4, RORA, JUN, FGL2, ZEB2, GNLY, FTL, SMAD3, IL7R, KIR2DL1, CTSD, BTG2, CCL5, HLA, RETN, CTSZ, and NCF2 were potential key genes associated with obese PCOS were identified. The proportions of T, B, and natural killer cells were higher in patients with PCOS compared to healthy women, with even higher proportions observed in obese patients with PCOS. Gene ontology and the Kyoto encyclopedia of genes and genomes analysis depicted that the differentially expressed genes were related to immune regulation pathways. Network pharmacology analysis identified that the key active components in CFDT were quercetin, carvacrol, β-sitosterol, cholesterol, and nobiletin, and TP53, AKT1, STAT3, JUN, SRC, etc. were the core targets. The core targets and their enrichment pathways overlapped with those in Part 1. Clinical trials in Part 3 found that CFDT reduced the dosage of gonadotropins use in patients with PCOS, increased the number of high-quality embryos, and improved the ongoing pregnancy rate. CFDT can improve the immune microenvironment of patients to some extent, reduce their economic burden, and enhance IVF outcomes. The improvement in the immune microenvironment in obese patients with PCOS may be linked to targets such as JUN and AKT.

Does hCG-trigger in the mild stimulation protocol for endometrial preparation have any effect on pregnancy outcome in frozen-thawed embryo transfer?

BackgroundRecent literature has explored the role of human chorionic gonadotropin (hCG) triggering in frozen embryo transfer (FET) cycles with natural endometrial preparation. Despite this, the impact of hCG triggering on pregnancy outcomes following endometrial preparation with mild stimulation (mST) using Letrozole and Gonadotropins remains inadequately characterized. This study aimed to elucidate the effects of hCG-trigger on pregnancy outcomes in mST-FET cycles.MethodsIn the present retrospective cohort study, the pregnancy outcomes of 409 eligible patients who underwent FET cycles with endometrial preparation using a mild ovarian stimulation protocol by letrozole plus low dose gonadotropins at the Royan Institute between 2020 and 2022, were investigated. The study population were segregated into two distinct groups according to type of ovulation: the spontaneous ovulation group (n = 138) and the hCG-trigger group (n = 271). The pregnancy outcomes including implantation and clinical pregnancy rates (CPR) and live birth rates (LBR) were compared between two groups. The multivariable logistic regression was performed to detect the most significant variables related to the LBR in the mST-FET cycles.ResultsDemographic and baseline characteristics were comparable between groups. No significant difference was found in terms of implantation rate (0.65 ± 0.32 vs. 0.60 ± 0.30, P-value: 0.31), CPR (37% vs. 39.7%, P-value: 0.53), and LBR (35.5% vs. 37.3%, P-value: 0.74) in the spontaneous ovulation and hCG-trigger groups, respectively. The logistic regression analysis revealed that only the stage of the transferred embryo exhibited a significant relationship with LBR (blastocyst vs. cleavage: odds ratio (OR); 2.33, 95% confidence interval (CI):1.41–3.86, P-value = 0.001).ConclusionPregnancy outcomes in the mST-FET cycles, including implantation rate, CPR, and LBR are comparable in cycles with or without hCG triggering. Based on the findings from multivariate regression analysis, the sole significant predictive factor for the LBR was the transfer of blastocyst embryos. It is recommended that these results be examined and discussed in future prospective studies with a larger sample size, considering the lack of comparable research in this field.

Factors affecting the outcomes of in vitro fertilization in women with endometriosis: Preliminary data from Vietnam

Objectives: This study aimed to assess the efficacy of in vitro fertilization (IVF) in patients with endometriosis and identify related factors that may influence treatment outcomes. Methods: This retrospective descriptive study was conducted between November 2018 and November 2022. The study group comprised individuals who were diagnosed with endometriosis (endometrioma and/or adenomyosis) indicated for in vitro fertilization. The control group (129 patients with 249 cycles), which included patients without endometriosis and had an equivalent mean age as the study group patients. Results: In the endometriosis group, the quantities of retrieved oocytes and Anti-Müllerian Hormone (AMH) were reduced compared to the control group. The overall dose of gonadotropin and the duration of ovarian stimulation were significantly higher than the control group. The endometriosis group exhibited a Metaphase II (MII) oocyte rate of 82.3% and an oocyte fertilization rate of 82.2%. However, in patients with endometriosis, the rates of implantation, clinical pregnancy, and ongoing pregnancy were significantly lower than in patients without endometriosis. Besides, the clinical pregnancy rate of women with endometriosis was remarkably higher in the groups with maternal age ⩽35 years, a ratio of Follicle-stimulating Hormone to Luteinizing Hormone (FSH/LH) ⩽1.5, and over 10 retrieved oocytes. Conclusion: Endometriosis was associated with a decreased rate of implantation, clinical pregnancy, and ongoing pregnancy after in vitro fertilization treatment compared with patients without endometriosis. In vitro fertilization outcomes in patients with endometriosis were influenced by maternal age ⩽35 years, FSH/LH ratio ⩽1.5, and number of retrieved oocytes over 10.

Double Ovarian Stimulation Versus Using Antagonist with a High Dose of Gonadotropin in Women with Poor Ovarian Response: A Randomized Clinical Trial Study

Background: Poor Ovarian Response (POR) to ovarian stimulation is a challenging factor in Assisted Reproduction Technology (ART). This study aimed to compare the efficacy of a conventional antagonist with high doses of gonadotropin protocol with double stimulation protocol in females with POR. Methods: This randomized clinical trial study was conducted on 60 women aged >35 with PORS at the Avicenna Infertility Center, Tehran, Iran. The participants were randomly divided into 2 groups (n=30 /each). In group 1, from the second day of the menstrual cycle, gonadotropin started at a dose of 450-600 units. In group 2, the second day of the menstrual period began with Letrozole 5 mg every night and an oral tablet of Clomiphene citrate 50 mg every day, and from the fourth day started 150 units of gonadotrophin (Triptorelin, 0.2 mg). Results: In this study, at the end of the follicular phase, there was a significant correlation between protocol type and the number of Germinal Vesicles (GV) (p=0.04). The mean number of oocytes retrieved was 2.76±1.9 in the conventional method and 3.23±2.1 in the double stimulation group (p=0.90). The number of fertilized oocytes was 31 in the conventional protocol and 25 in the double stimulation protocol. The mean number of pregnancies that led to the fetus was 1.38±1.3 in the conventional protocol and 0.96±0.9 in the double stimulation group (p=0.018). Conclusion: The results of this study show that the embryos in the double-stimulation group were more capable of completing the pregnancy, and the double-stimulation group had a higher live birth rate.

Fixed versus flexible gonadotropin releasing hormone antagonist protocol in women with polycystic ovary syndrome undergoing in vitro fertilization: An RCT.

Despite the extensive use of the gonadotropin-releasing hormone (GnRH) antagonist protocol in treating infertile women, particularly those with polycystic ovary syndrome (PCOS), there have not been sufficient evidence to compare the flexible and fixed variants in in vitro fertilization (IVF) cycles. This study aims to assess the treatment outcomes of flexible and fixed types of GnRH-antagonist protocol for IVF in women with PCOS. In this randomized clinical trial, 150 infertile women with PCOS, who were candidates for IVF, and referred to the Yazd Research and Clinical Center for Infertility, Yazd, Iran between October 2023 and February 2024 were included. Participants were divided into 2 groups (n = 75/each) based on the type of antagonist protocol (fixed or flexible). GnRH antagonist administration started on the 5 day of gonadotropin treatment in the fixed group. In the flexible group when there was at least one follicle 12-14 mm, GnRH antagonist was started. Finally, the number of metaphase II oocyte, the quality of embryos, the duration of the stimulation cycle, the dose of gonadotropin, the number of GnRH-antagonist, and the rate of ovarian hyperstimulation syndrome were evaluated. No statistically significant difference was observed in terms of cycle length and the total dose of gonadotropin between groups. Nevertheless, a notable distinction was observed in the total number of oocytes (17.84 vs. 15.5, p = 0.023) and mature oocytes (13.64 vs. 11.83, p = 0.019) in the flexible group compared to the fixed group. In conclusion, the IVF outcomes are more favorable in women with PCOS undergoing the flexible GnRH-antagonist protocol compared to the fixed protocol.

The Effect of the Gonadotropin Dose Increment During Controlled Ovarian Hyperstimulation on Live Birth Rates of POSEIDON Group 3-4 Patients

This retrospective study seeks to explore whether modifying the gonadotropin dose in cases of poor ovarian response during controlled ovarian hyperstimulation contributes to improved live birth rates in Poseidon Group 3-4 patients. The study took place at a tertiary level university. The electronic database spanning 2012-2021 was scrutinized to identify patients with diminished ovarian reserve (DOR) who underwent intra-cytoplasmic sperm injection – embryo transfer (ICSI-ET). Diminished ovarian reserve was determined using the POSEIDON criteria. Patients were categorized into two groups based on whether dose adjustment was implemented during the initial ultrasound assessment in controlled ovarian hyperstimulation (COH). There were 188 patients in the dose adjustment (DA) group and 310 patients in the fixed-dose (FD) group. The demographic parameters were similar between the groups. The started gonadotropin dose was similar in both groups (300 IU). The median dose adjustment on the first control was +75 IU in the DA group. The follicle output rates, follicle to oocyte indexes, and the embryology parameters were comparable between the groups. The positive pregnancy rate was 19.7% (36/188) in the DA group vs. 19.1% (61/310) in the FD Group (p=0.4). The primary outcome of the study; live birth rates were 12% in the DA group vs. 9% in the FD group, and the results were statistically similar (p=0.3). Our research revealed that adjusting the gonadotropin dose in cases of inadequate ovarian response during COH results in comparable live birth rates to those observed in the fixed-dose group. For patients exhibiting an inadequate response, dose adjustment may be deemed necessary.

Impact of GnRH antagonist pretreatment on oocyte yield after ovarian stimulation: A retrospective analysis.

The study investigates whether a 3-day pretreatment course with a GnRH antagonist in the early follicular phase has an impact on the number of retrieved COCs in a GnRH antagonist stimulation protocol. This is a retrospective single center crossover study involving women who did not conceive after one GnRH antagonist stimulation cycle ("standard cycle") and proceeded with another GnRH antagonist stimulation cycle preceded by early administration of GnRH antagonist for 3 days ("pretreatment cycle") with fresh embryo transfer or frozen embryo transfer. 430 patients undergoing 860 cycles were included. The mean female age was 34.4 ± 4.8 years. Indications for fertility treatment included unexplained infertility (34.3%), male-factor infertility (33.3%), age (16.9%), PCOS (8.2%), tubal (4.7) and endometriosis (2.6%). All cycles were divided into two groups: group 1 (standard, 430 cycles) and group 2 (pretreatment, 430 cycles). The mean duration of stimulation was similar in both groups (10.3 vs 10.3 days, p = 0.28). The starting dose of gonadotropin (234.9 vs 196.8 IU, p<0.001), total amount of gonadotropin used (2419 vs 2020 IU, p<0.001), the total number of retrieved COCs (10 vs 7.8 p<0.001) and the number of mature oocytes (8 vs 5.8 p<0.001) were significantly higher in group 2 than in group 1. The Generalized estimating equation (GEE) regression analysis showed that the pretreatment strategy had a significant positive effect on the number of COCs (coefficient 2.4, p <0.001 after adjusting for known confounders (age, indication, stimulation dose, type, and duration of stimulation). In conclusion, A 3-day course of GnRH antagonist pretreatment increases the number of COCs obtained after ovarian stimulation.

Effects of ovarian stimulation on embryo euploidy: an analysis of 12874 oocytes and 3106 blastocysts in cycles with preimplantation genetic testing for monogenic disorders.

Does ovarian stimulation and the ovarian response affect embryo euploidy? Ovarian stimulation and the ovarian response in women undergoing preimplantation genetic testing for monogenic disorders (PGT-M) cycles did not affect the rates of blastocyst euploidy. Whether or not ovarian stimulation in IVF-embryo transfer has potential effects on embryo euploidy is controversial among studies for several reasons: (i) heterogeneity of the study populations, (ii) biopsies being performed at different stages of embryo development and (iii) evolution of the platforms utilized for ploidy assessment. Patients who undergo PGT-M cycles typically have no additional risks of aneuploidy, providing an ideal study population for exploring this issue. A retrospective cohort study including embryos undergoing PGT-M was conducted at a single academically affiliated fertility clinic between June 2014 and July 2021. A total of 617 women with 867 PGT-M cycles involving 12874 retrieved oocytes and 3106 trophectoderm biopsies of blastocysts were included. The primary outcome of the study was median euploidy rate, which was calculated by dividing the number of euploid blastocysts by the total number of biopsied blastocysts for each cycle. Secondary outcomes included the median normal fertilization rate (two-pronuclear (2PN) embryos/metaphase II oocytes) and median blastulation rate (blastocyst numbers/2PN embryos). Comparable euploidy rates and fertilization rates were observed across all age groups, regardless of variations in ovarian stimulation protocols, gonadotropin dosages (both the starting and total dosages), stimulation durations, the inclusion of human menopausal gonadotrophin supplementation, or the number of oocytes retrieved (all P > 0.05). Blastulation rates declined with increasing starting doses of gonadotropins in women aged 31-34 years old (P = 0.005) but increased with increasing gonadotrophin starting doses in women aged 35-37 years old (P = 0.017). In women aged 31-34, 35-37, and 38-40 years old, blastulation rates were significantly reduced with increases in the number of oocytes retrieved (P = 0.001, <0.001, and 0.012, respectively). Limitations include the study's retrospective nature and the relatively small number of patients of advanced age, especially patients older than 40 years old, leading to quite low statistical power. Second, as we considered euploidy rates as outcome measures, we did not analyze the effects of ovarian stimulation on uniform aneuploidy and mosaicism, respectively. Finally, we did not consider the effects of paternal characteristics on embryo euploidy status due to the fact that blastocyst aneuploidy primarily originates from maternal meiosis. However, sperm factors might have an effect on embryo development and the blastulation rate, and therefore also the number of blastocysts analyzed. The exclusion of patients with severe teratozoospermia and the fact that only ICSI was used as the insemination technique for women undergoing PGT-M contributed to minimize the effect of paternal factors. Ovarian stimulation and response to stimulation did not affect blastocyst euploidy rates in women undergoing PGT-M cycles. However, in women aged 31-40 years old, there was a significant decline in blastulation rates as the number of retrieved oocytes increased. This study was supported by the National Natural Science Foundation of China (Grant No. 81701407, 82301826); the National Key Research and Development Program of China (2022YFC2702901, 2022YFC2703004); China Postdoctoral Science Foundation (2022M710261), and China Postdoctoral Innovation Talent Support Program (BX20220020). There is no conflict of interest. N/A.

In-vitro fertilization experience with follitropin-delta in poor responders identified by POSEIDON Classification.

Controlled ovarian stimulation during in-vitro fertilization (IVF) is personalized based on anticipated hyper, normal, poor response. With respect to poor responders, who are often treated using higher gonadotropin dosing and combination of urinary and recombinant gonadotropins (rFSH) with marginal benefit, we report our experience with a newer, more potent rFSH (Follitropin-δ) undergoing IVF. Retrospective analysis of all IVF cycles in which follitropin-δ was used alone or combined with urinary gonadotropins over a 3-year period. Patients were grouped according to the POSEIDON Classification as expected low responders (POSEIDON 3-4; AMH<1.2; N.=45), unexpected low responders (POSEIDON 1-2; retrieval of ≤9 oocytes; N.=67) and those with a normal response (N.=93). Demographic, stimulation (including target number of retrieved oocytes [8 to14]), embryology and clinical outcome parameters (clinical pregnancy rate [CPR], live birth rate [LBR], cumulative live birth rate [cLBR]) were compared. Those categorized as POSEIDON patients were older, had lower ovarian reserve, were more likely to use a mixed protocol, less likely to reach the target oocytes retrieved (35.7% vs. 51.6%, P<0.001), and had a lower cLBR per patient (29.5% vs. 38.7%, P=0.006) when compared to non-POSEIDON patients. Expected low responders (POSEIDON 3-4) were older and had lower AMH when compared to unexpected low responders (POSEIDON 1-2), but no differences in the target of oocytes retrieved (33.3% vs. 37.3%, P=0.66) and cLBR (28.9% vs. 37.3%, P=0.06) were noted. In expected low responders, follitropin-δ can be used to optimize oocyte collection and clinical outcome though one may need to deviate from the algorithm-suggested dose. Future studies should explore stimulation modifications in unexpected low responders.

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 &lt;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 &gt; 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.

The effects of growth hormone supplementation in poor ovarian responders undergoing In vitro fertilization or Intracytoplasmic sperm injection: A systematic review and meta-analysis of randomized controlled trials.

To evaluate the effect of growth hormone (GH) supplementation on outcomes of in vitro fertilization (IVF) or Intracytoplasmic sperm injection (ICSI) for women with poor ovarian response. Relevant randomized controlled trials (RCTs) were obtained through search in several databases including PubMed, Scopus, Clinicaltrials.gov, Google Scholar, and Cochrane Library. Outcome measures included live birth rate, clinical pregnancy rate, cycle cancelation rate, number of retrieved oocytes, number of transferred embryos, total dose of gonadotropin, duration of gonadotropin treatment, and peak estradiol level. Additionally, a meta-regression analysis was carried out to determine any potential linear relationships between these outcomes and IVF success. After analyzing 18 RCTs comprising of 1870 patients, the study found that GH supplementation improved the number of retrieved oocytes [standardized mean difference (SMD), 0.65; 95% confidence interval (CI), 0.29-1.00] and transferred embryos group (SMD, 0.80, 95% CI, 0.39, 1.21) as well as peak E2 level (SMD, 1.20; 95% CI, 0.59, 1.81). While reduced the total dose and duration of gonadotropin treatment (SMD, -0.82, 95% CI, -1.25, -0.39, and SMD, -0.63, 95% CI, -1.04, -0.22, respectively). The meta-regression analysis found no linear relationship between clinical pregnancy, live birth rate, or cycle cancelation rate and the outcomes measured (p>0.1). Based on the available evidence, GH supplementation appears to improve the outcomes of IVF or ICSI in women with poor response. However, there is a need for further RCTs with larger sample sizes to determine the cost-effectiveness of adding GH to conventional protocols of IVF/ICSI for treating infertility in women with poor ovarian response.

Significance of FSHR and LHCGR gene polymorphisms on clinical outcomes in gonadotropin-releasing hormone antagonist protocol with freeze-all strategy: A case-control study.

Follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/choriogonadotropin receptor (LHCGR) are integral to ovarian function, facilitating follicle development and maturation through their respective hormonal interactions. The influence of receptor polymorphisms on the outcomes of freeze-all cycles remains unclear. This study investigates the impact of FSHR N680S and LHCGR N312S polymorphisms on clinical outcomes in freeze-all cycles. Women undergoing controlled ovarian stimulation for assisted reproductive technology participated in this study. They were administered a gonadotropin-releasing hormone antagonist protocol, with recombinant follicle-stimulating hormone (rFSH) dosages adjusted according to age, body mass index, antral follicle count, and individual hormonal responses. Additionally, human menopausal gonadotropin dosages were tailored based on the LHCGR N312S genetic variant. Analysis revealed no significant differences in age, body mass index, antral follicle count, or marital status across the genotypes of FSHR N680S and LHCGR N312S. However, notable differences were observed in the rFSH dosage required daily and in total among the FSHR polymorphism genotypes. Genotypes of the LHCGR polymorphism correlated with fewer stimulation days. A significant interaction was observed between the 2 polymorphisms concerning total rFSH dosage. The presence of serine in the FSHR polymorphism was associated with higher rFSH dosage requirements. Both FSHR N680S and LHCGR N312S polymorphisms significantly influenced clinical pregnancy and live birth outcomes in freeze-all cycles, underscoring the potential of a pharmacogenomic approach to optimize hormone supplementation in controlled ovarian stimulation protocols during assisted reproductive technology treatments.

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.

New Immunological Indexes for the Effect of Systemic Inflammation on Oocyte and Embryo Development in Women With Unexplained Infertility: Systemic Immune Response Index and Pan-Immune-Inflammation Value.

Predicting the impact of systemic inflammation on oocyte and embryonic development in unexplained infertile women using the new immunological indexes. This retrospective cohort study was conducted using the records of the In Vitro Fertilization Department of Ankara Gülhane Training and Research Hospital. After reviewing the records of patients who had undergone in vitro fertilization (IVF) for unexplained infertility (UI) and excluding all known factors that could cause systemic immune inflammation, the systemic immune response index (SIRI), and pan-immune score were calculated from the pre-treatment hemogram parameters between the embryo arrest (EA) group and the embryo transfer group. It was investigated whether there was a statistical difference between the two groups and whether an SIRI value affecting embryo quality was found. A receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off values for inflammatory markers to predict EA. The 108 EA group (embryos that were arrested during their development and could not be transferred) and the 140 embryo transfer group showed statistically significant differences in the parameters of systemic inflammatory index (SII), SIRI, pan-immune inflammation value (PIV), and neutrophil/lymphocyte ratio (NLR) (p < 0.05). These inflammatory parameters, which were examined before ovulation induction, also correlated positively with the required total dose of gonadotropin and negatively with the ovarian sensitivity index (OSI). SII, SIRI, PIV, and NLR have specific cut-off values with ROC analysis and determine the effect of the inflammatory status of the environment in which the oocyte develops on EA (p < 0.005). In women with UI, high levels of systemic immune inflammation have a negative impact on oocyte and embryo development, and treatments to suppress inflammation may improve IVF success.

Effect of PG-600 dose in cows with persistent corpus luteum treated with PGF2α and hCG

The purpose of this study was to determine the effect of administering a dose of gonadotropin (PG-600) in cows with persistent corpus luteum (PCL) which were treated with prostaglandin F2 α (PGF2α) and human chorionic gonadotropin (hCG). This study used 20, three-year-old cows diagnosed with PCL, had recently given birth, and were not pregnant. Cows were randomly allocated into groups T0, T1, T2 and T3. Cows in all groups were injected with PGF2α (25 mg/cow). Simultaneously, cows in groups T1, T2 and T3 were also injected with PG-600 at doses of 100, 150 and 200 IU/cow respectively. PGF2α and PG-600 were injected when PCL was identified. After that, cows showing signs of estrus were injected with hCG (100 IU/cow) and artificially inseminated 12-18 hours after the appearance of signs of estrus. AI was conducted using frozen thawed semen. Sixty days following AI, a pregnancy examination was conducted using USG. Estrus was detected in all treated cows, while the pregnancy rates varied. Compared with other groups, the groups given 100 and 150 IU PG-600 produced higher pregnancy rates. It could be concluded that the combination of 25 mg PGF2α, 150 IU PG-600, and 100 IU hCG was the most effective treatment to produce high pregnancy rates in cows with persistent corpus luteum.

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.

A new decision-support tool in a multi-center randomized trial for personalized, optimized, and simplified fertility treatment in non-PCOS patients.

This study aimed to evaluate the effectiveness of a clinical decision support tool, Opt-IVF, in achieving the following outcomes: reducing the total cumulative dosage of Gonadotropins (Gns) used during controlled ovarian stimulation cycles and reducing the repeated ultrasonograms (USG) for monitoring follicular growth without compromising the number of good quality blastocysts obtained. The study design employed a multi-center randomized trial. The study enrolled 115 women aged 25-45 years undergoing IVF. Among the participants, 55 were randomly assigned to the intervention group (Opt-IVF), and 60 were randomly assigned to the control group. The intervention involved using a clinical decision support tool, Opt-IVF, to guide Gn dosing and trigger dates. The participants in the intervention group required significantly lower cumulative Gn dosage. The intervention group had higher numbers of oocytes retrieved and M2 retrieved than the control group. The number of good-quality blastocysts, the good-quality blastocyst rate, the ovarian sensitivity index (OSI), and the pregnancy rate in the intervention group were significantly higher than in the control group. The utilization of the clinical decision support tool led to several positive outcomes, including eliminating the need for ultrasound exams after day 5, reducing the dosage of Gn required, and yielding significantly higher numbers of high-quality blastocysts and higher pregnancy rates. Thus, Opt-IVF can successfully provide a personalized, optimized, and simplified approach to superovulation. Opt-IVF consistently outperformed the clinical teams in most of the outcomes. Clinical trials registration: ClinicalTrials.gov (ID - NCT05811065). Date of Registration: 15 March 2023. Date of enrollment of the first subject: 20 March 2023. The high cost of IVF is a result of costly drugs, fixed prices for infrastructure, extensive testing required, and labor costs for physicians and other healthcare personnel. Superovulation, which involves the drug-induced release of multiple eggs needed for IVF, accounts for a significant share of these costs. Current approaches to superovulation involve almost daily monitoring of follicle development using ultrasound and/or blood tests. The daily dosage of stimulatory hormones is then prescribed by physicians based on empirical data and clinical experience. However, the dose is not optimized for each patient, and overstimulation complications can occur. The cost of testing and drugs makes this stage very expensive. To overcome the shortcomings of this system, we have developed a decision support tool (Opt-IVF) that can provide a personalized model-optimized dosage profile for each patient. The clinical results show that Opt-IVF optimizes and personalizes dosage, reduces testing, and provides better outcomes for patients.

Evaluation of ovarian reserve and the assisted reproductive technology (ART) cycles’ outcome as well as the relapse rate within one year after ART in women with multiple sclerosis: a case-control study

ObjectiveTo compare the ovarian reserve and the results of infertility treatment, as well as to investigate the relapse rate in the first year after the assisted reproductive technology (ART) cycle in patients with multiple sclerosis (MS) referred to Royan Institute.Materials and methodsThis retrospective study was carried out to evaluate all women diagnosed with MS and referred to Royan Institute for assessment and treatment of possible infertility between 2011 and 2022. The control group consisted of randomly selected healthy women with tubal factor infertility who were referred for treatment during the same time period and matched in terms of age. A comparison was made between groups in terms of ovarian reserve and infertility treatment outcomes. Additionally, patients with MS who met the criteria were monitored via telephone to evaluate the symptoms, disability and relapse rate both pre- and post-ART.ResultsOver the course of a decade, the database documented a total of 60 cases diagnosed with MS. Upon examination of the records, it was found that in 27 patients only admission was done without any hormonal assessment or infertility treatment cycle and 5 patients proceeded with the intrauterine insemination cycle. Eventually, 28 women with MS underwent the ART cycle and all of them were treated with interferon beta, glatiramer acetate, or some oral disease modifying therapies. No statistically significant difference in terms of the basal levels of luteinizing hormone, follicle-stimulating hormone and anti-Müllerian hormone was found between the MS and control groups (P > 0.05). Two groups were comparable in terms of menstrual status. The study revealed that both groups exhibited similarities in terms of the controlled ovarian stimulation protocol and duration, the dosage of gonadotropin administered, as well as the ovarian response type, clinical pregnancy rate, and live birth rate (P > 0.05). After follow up, only 2 patients (9.5%) reported relapse of symptoms within one year after ART.ConclusionThe ovarian reserve and ovarian stimulation cycle and pregnancy outcomes following the ART cycle in MS patients were similar to the age-matched control group. The relapse rate of multiple sclerosis did not show a significant increase within a year following the ART cycle.

Competence of Combined Low Dose of Human Chorionic Gonadotropin (HCG) and Clomiphene Citrate (CC) Versus Continued CC during Ovulation Induction in Women with CC-Resistant Polycystic Ovarian Syndrome: A Randomized Controlled Trial.

Background and Objectives: Polycystic ovarian syndrome (PCOS) is a widespread endocrine disorder affecting 5-18% of females in their childbearing age. The aim of this study is to assess the efficacy of combining a low dosage of human chorionic gonadotropin (HCG) along with clomiphene citrate (CC) for stimulating ovulation in infertile women diagnosed with CC-resistant PCOS. Materials and Methods: A randomized controlled trial was carried out on 300 infertile CC-resistant PCOS women. All participants were assigned to two groups: the CC-HCG group and the CC-Placebo group. Subjects in the CC-HCG group were given CC (150 mg/day for 5 days starting on the 2nd day of the cycle) and HCG (200 IU/day SC starting on the 7th day of the cycle). Subjects in the CC-Placebo group were given CC and a placebo. The number of ovarian follicles > 18 mm, cycle cancellation rate, endometrial thickness, ovulation rate, clinical pregnancy rate, and occurrence of early ovarian hyper-stimulation syndrome were all outcome variables in the primary research. Results: Data from 138 individuals in the CC-HCG group and 131 participants in the CC-Placebo group were subjected to final analysis. In comparison to the CC-Placebo group, the cycle cancellation rate in the CC-HCG group was considerably lower. The CC-HCG group exhibited a substantial increase in ovarian follicles reaching > 18 mm, endometrial thickness, and ovulation rate. The clinical pregnancy rate was higher in the CC-HCG group (7.2% vs. 2.3%; CC-HCG vs. CC-Placebo). Upon adjusting for BMI and age, the findings of our study revealed that individuals in the CC-HCG group who had serum prolactin levels below 20 (ng/mL), secondary infertility, infertility duration less than 4 years, baseline LH/FSH ratios below 1.5, and serum AMH levels more than 4 (ng/mL) had a higher likelihood of achieving pregnancy. In the CC-Placebo group, there was a greater prediction of clinical pregnancy for those with serum AMH (<4), primary infertility, serum prolactin ≤ 20 (ng/mL), baseline LH/FSH < 1.5, and infertility duration < 4 years. Conclusions: The use of a small dose of HCG along with CC appeared to be an effective treatment in reducing cycle cancelation, improving the clinical pregnancy rate and ovulation rate in CC-resistant PCOS patients. The trial was registered with Clinical Trials.gov, identifier NCT02436226.