The press-assisted fusion scheme significantly mitigates the quantity of HVJ-E required in mitochondrial replacement techniques.

In brief: The impact of HVJ-E employed in mitochondrial replacement techniques (MRTs) on embryonic development remains uncertain. This study has exhibited the influence of HVJ-E utilized in MRTs on embryonic development and has devised a novel HVJ-E-induced fusion approach to curtail the amount of HVJ-E employed in MRTs. Abstract: Mitochondrial replacement techniques (MRTs) provide a viable option for women carrying pathogenic mitochondrial DNA (mtDNA) variants to conceive disease-free offspring with a genetic connection. In comparison to electrofusion, HVJ-E-induced fusion has been identified as the most promising approach for clinical translation of MRTs due to its absence of electrical interference. However, despite confirmation of the absence of RNA activity in HVJ-E, a reduction in blastocyst quality has been observed in various MRTs studies utilizing the HVJ-E-induced fusion scheme. Recent investigations have revealed a dose-dependent elevation of reactive oxygen species (ROS) levels in various cancer cells incubated with HVJ-E. However, the impact of HVJ-E as a sole determinant on embryonic development in MRTs remains unverified. This investigation establishes that the augmented concentration of HVJ-E utilized in the conventional HVJ-E fusion protocol is an autonomous variable that influences embryonic development in MRTs. This effect may be attributed to amplified DNA damage resulting from heightened levels of ROS in reconstructed embryos. To mitigate the presence of HVJ-E in reconstructed zygotes while maintaining optimal fusion efficiency in MRTs, a novel HVJ-E-induced fusion approach was devised, namely, press-assisted fusion. This technique offers potential advantages in reducing detrimental factors that impede embryo development in MRTs.

The effect of gonadotrophin-releasing hormone agonist versus human chorionic gonadotrophin trigger on pregnancy and neonatal outcomes in Letrozole-HMG IUI cycles.

BACKGROUND: GnRHa and hCG are both used for oocyte maturation and ovulation triggering. However, GnRHa have a shorter half-life than hCG, which leads to luteal phase deficiency. Letrozole (LE) has been found to improve the luteal function. Thus, the choice of triggering strategy can be different in intrauterine insemination (IUI) cycles using LE and human menopausal gonadotropin (HMG). The aim of this study was to compare the pregnancy and neonatal outcomes of patients triggered with GnRHa versus hCG versus dual trigger in LE-IUI cycles. METHODS: This retrospective cohort study included 6,075 LE-HMG IUI cycles between January 2010 and May 2021 at a tertiary-care academic medical center in China. All cycles were divided into three groups according to different trigger strategies as hCG trigger group, GnRHa trigger group and dual trigger group. The primary outcome was clinical pregnancy rate. Logistic regression analysis was performed to explore other risk factors for clinical pregnancy rate. RESULTS: No significant difference was observed in clinical pregnancy rate between hCG, GnRHa and dual trigger cycles in LE-HMG IUI cycles (P = 0.964). The miscarriage rate was significantly lower in the GnRHa trigger group, and higher in the dual trigger group, compared with the hCG group (P = 0.045). Logistic analysis confirmed that triggering strategy was associated with miscarriage (aOR:0.427, 95%CI: 0.183-0.996, P = 0.049; aOR:0.298, 95%CI: 0.128-0.693, P = 0.005). No significant differences were observed regarding neonatal outcomes between the three groups. CONCLUSIONS: Our findings suggested that both GnRHa and dual trigger can be used to trigger ovulation in LE-HMG IUI cycles, but dual trigger must be used with caution.

Optimal lead follicle size in letrozole human menopausal gonadotrophin intrauterine insemination cycles with and without spontaneous LH surge.

RESEARCH QUESTION: What is the optimal lead follicle size in letrozole, human menopausal gonadotrophin and intrauterine insemination (IUI) cycles with and without spontaneous LH surges? DESIGN: This retrospective cohort study included 3797 letrozole HMG IUI cycles between January 2010 and May 2021. All cycles were divided into two groups: the HCG trigger group (trigger day LH ≤15 mIU/ml) and the spontaneous LH surge group (trigger day LH >15 mIU/ml). These two groups were subdivided into smaller groups based on the diameter of the follicles. The primary outcome measure was clinical pregnancy rate. Logistic regression analysis was conducted to explore other risk factors. RESULTS: In the HCG trigger group, the clinical pregnancy rate varied significantly, with rates of 20.8%, 14.9% and 11.8% for the 16.1-18.0, 18.1-20.0 and 20.1-22.0 mm groups, respectively (P = 0.005). In the spontaneous LH surge group, the pregnancy rate of follicles within 14.1-16.0 mm was significantly higher than that of follicles within 20.1-22.0 mm (adjusted OR 0.533, 95% CI 0.308 to 0.923, P = 0.025). Also, patients with two lead follicles were 2.569 times more likely to achieve a clinical pregnancy than those with only one lead follicle (adjusted OR 2.569, 95% CI 1.258 to 5.246, P = 0.010). The duration of infertility was also found to be a common influencing factor in both groups. CONCLUSIONS: The optimal lead follicle size was between 16.1 and 18.0 mm in HCG-triggered letrozole HMG IUI cycles. If the lead follicle size is relatively small (14.1-18.0 mm) when a spontaneous LH surge occurs, there is no need to cancel the IUI cycle.

Reproductive endocrine characteristics and in vitro fertilization treatment of female patients with partial 17α-hydroxylase deficiency: Two pedigree investigations and a literature review.

Background: 17α-hydroxylase/17, 20-lyase deficiency (17-OHD) is caused by the mutations of the CYP17A1 gene. The classical phenotype of 17-OHD includes hypertension, hypokalemia, and abnormal sexual development, with partial 17-OHD typically less severe than the complete deficiency. Infertility is always one of the main clinical manifestations of partial 17-OHD. However, to date, the pregnancy potentials of partial 17-OHD female patients have rarely been investigated, and few live-birth cases have been reported among them. Moreover, the reproductive endocrine characteristics of partial 17-OHD female patients have not been completely clarified and the treatment skills of in vitro fertilization and embryo transfer (IVF-ET) have not been well summarized yet. Methods: Two Chinese infertile female patients clinically diagnosed as partial 17-OHD were enrolled and their pedigree investigations were performed. Hormones were determined to depict the endocrine conditions of partial 17-OHD female patients. The adrenocorticotropic hormone (ACTH) stimulation test was performed to evaluate the functions of the adrenal cortex. Genotype analysis was conducted by next-generation sequencing (NGS) and Sanger sequencing was used to verify the results. IVF-ET was performed for the treatment of their infertility. Specifically, the progestin-primed ovarian stimulation (PPOS) protocol was chosen for the controlled ovarian hyperstimulation (COH) cycles, and the hormone replacement treatment (HRT) protocol was adopted for the endometrial preparation in frozen-thawed embryo transfer (FET) cycles. Results: Hormone assays revealed a reduced estradiol (E2) and testosterone (T) level, and an elevated progesterone (P4) level. The classic ACTH stimulating test evidenced a suboptimal response of cortisol to ACTH. Genotype analysis demonstrated that the proband1 carried two variants: c.1459_1467del (p.Asp487_Phe489del)het and c.995T>C (p.lle332Thr)het. The proband2 was found to be a homozygote with the mutation of c.1358T>A (p.Phe453Ser)hom. The two female patients both succeeded in pregnancy and delivery of healthy babies through IVF-ET, with the usage of PPOS, HRT, and low-dose glucocorticoids. Conclusions: Partial 17-OHD female patients manifested menstrual cycle disorders and infertility clinically; displayed high P4 and low E2 and T; showed sparse pubic hair in physical examinations; and revealed multiple ovarian cysts in ultrasonic visualization. Moreover, the pregnancy potentials of infertile partial 17-OHD women seemed to increase with the adoption of IVF-ET. Considering the sustained elevated P4 level, PPOS is a feasible protocol for them in COH.

The pregnancy outcomes of infertile women with polycystic ovary syndrome undergoing intrauterine insemination with different attempts of previous ovulation induction.

Background: Polycystic ovary syndrome (PCOS) is one of the most common reasons for infertility. The consensus of the treatment of infertile women with PCOS is ovulation induction (OI) for six to nine attempts before in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Nowadays, more attention was paid to a rising, noninvasive treatment, intrauterine insemination (IUI), as some experts claimed IUI could benefit PCOS patients with infertility. Our study means to investigate the outcomes of IUI for PCOS patients and if patients' previous OI cycles can be a predictive factor for IUI outcomes. Methods: A total of 1,086 PCOS patients was included and 1,868 IUI cycles were performed between January 2007 and July 2021 in the department of assisted reproduction in Shanghai Ninth People's Hospital. All included patients underwent IUI treatments with letrozole+human menopausal gonadotropin (LE+hMG) for ovarian stimulation. Results: The pregnancy outcomes were not associated with the attempts of failed OI cycles previously. Specifically, the clinical pregnancy rate was 21.14% for PCOS patients without previous OI cycles, 21.95% for PCOS patients with 1-2 previous OI cycles and 23.64% for PCOS patients with 3 or more previous OI cycles (p=0.507). The corresponding live birth rate was 16.64%, 18.06%, and 18.68%, respectively, of which the difference was not statistically significant (p=0.627). The cumulative rate per patient was 38.59% for clinical pregnancy and 31.03% for live birth, and approximately 98% of the pregnancies occurred in the first 3 cycles of IUI. Conclusion: PCOS women with different attempts of OI cycles had similar pregnancy outcomes after IUI, thus a history of repeated failures of OI treatments was not a predictive factor for the pregnancy outcomes in IUI cycles. Most pregnancies occurred in the first three cycles of IUI, so we strongly recommended three attempts of IUI for PCOS women before they switched to IVF/ICSI. Generally, IUI might be an assist for infertile women with PCOS before IVF/ICSI and might accelerate pregnancy for target women without invasive manipulations.

A follow-up study on congenital anomalies in 2208 offspring of three years old born after luteal-phase stimulation.

RESEARCH QUESTION: What is the long-term safety in terms of congenital anomalies of a luteal-phase stimulation (LPS) protocol? DESIGN: In this cohort study, 664 couples and their children born after LPS and 1308 couples and their children born after a short agonist protocol were recruited. To investigate the long-term safety of LPS in terms of the prevalence of congenital anomalies, the physical growth and the health status of the offspring, the follow-up was divided into three steps: preparations before follow-up, first-stage follow-up including four telephone interviews, and second-stage follow-up when the children were aged 3 years. RESULTS: The total prevalence of congenital anomalies did not differ between groups. The detailed classification showed a significantly lower percentage of musculoskeletal system congenital anomalies in singletons (P = 0.020) and an obviously higher percentage of digestive system congenital anomalies in multiple births (P = 0.028), both in the LPS group. In the evaluation of physical growth and health status, no significant differences were discovered between the two groups. CONCLUSIONS: This study showed that offspring born after the LPS protocol did not exhibit an elevated rate of total congenital anomalies up to the age of 3. In addition, indicators regarding physical growth and health status were broadly similar between the two groups. These results have preliminarily confirmed the long-term safety of LPS. A subsequent long-term follow-up with a larger sample size should be carried out to generate more convincing evidence and more accurate conclusions.

The impact of blastomere loss on pregnancy and neonatal outcomes of vitrified-warmed Day3 embryos in single embryo transfer cycles.

BACKGROUND: Blastomere loss is a common phenomenon that occurs following cryopreservation. To date, studies have drawn conflicting conclusions regarding the impact of blastomere loss on pregnancy outcomes. Besides, limited information is available concerning the neonatal safety of embryos with blastomere loss. In the present study, we aimed to investigate the impact of blastomere loss on pregnancy and neonatal outcomes of vitrified/warmed Day3 cleavage-stage embryos in single embryo transfer cycles. METHODS: This retrospective cohort study included all vitrified/warmed D3 cleavage-stage single frozen-thawed embryo transfer (FET) cycles between April 2015 and February 2021. We compared pregnancy and subsequent neonatal outcomes between the intact embryos group and the blastomere loss group in single FET cycles. RESULTS: A total of 6287 single FET cycles were included in the study, in which 5873 cycles were classified into the intact embryo group and 414 cycles were classified into the blastomere loss group. The outcomes of the blastomere loss group were significantly inferior to those of the intact embryo group, in terms of implantation/biochemical pregnancy/clinical pregnancy/ongoing pregnancy rate and live birth rate per embryo transfer cycle/per clinical pregnancy. Further binary logistic regression confirmed that blastomere loss was negatively associated with live birth. Moreover, the blastomere loss group presented with an elevated early miscarriage rate. The neonatal conditions were broadly similar between the two groups. Additionally, multiple binary logistic regression analysis demonstrated that primary infertility and intracytoplasmic sperm injection (ICSI) were common influencing factors of blastomere loss (aOR 1.447, 95% CI 1.038-2.019, P = 0.029; aOR: 1.388, 95% CI: 1.044-51.846, P = 0.024). CONCLUSIONS: The transfer of vitrified/warmed D3 embryos with blastomere loss is related to impaired embryo developmental potentials and reduced probabilities of conception. Moreover, even if the embryos with blastomere loss have implanted and reached clinical pregnancies, they present with a lower possibility of developing to live birth owing to a higher early miscarriage rate. However, once the embryos with blastomere loss result in a live birth, no adverse neonatal outcomes are observed. Primary infertility and ICSI were found to be risk factors for blastomere loss.

The Effect of Spontaneous LH Surges on Pregnancy Outcomes in Patients Undergoing Letrozole-HMG IUI: A Retrospective Analysis of 6,285 Cycles.

Background: To date, no consensus has been reached on whether to wait for spontaneous luteinizing hormone (LH) surge to occur or to trigger ovulation regardless of the presence of an LH surge for achieving higher success rate in intrauterine insemination (IUI) cycles. Therefore, we hope to investigate the effect of the presence of a spontaneous LH surge on pregnancy outcomes in letrozole-human menopausal gonadotropin (LE-HMG) IUI cycles. Methods: In this retrospective cohort study, a total of 6,285 LE-HMG IUI cycles were included between January 2010 and May 2021. Cycles were categorized into three groups: the trigger + LH surge group, the trigger only group, and the LH surge only group. The primary outcome measure was the clinical pregnancy rate. A logistic regression analysis was performed to explore other risk factors affecting the clinical pregnancy rate. Results: No significant differences were observed in biochemical pregnancy rate (P =0.640), clinical pregnancy rate (P =0.702), ongoing pregnancy rate (P =0.842), and live birth rate (P =0.951) among the three groups. The binary logistic regression analysis also confirmed that the existence of an LH surge was not associated with clinical pregnancy. There was a difference in ectopic pregnancy rates (P =0.045), but logistic regression showed that the presence of a spontaneous LH surge has no association with ectopic pregnancy. Nonetheless, patients with lead follicles within 18.1-20.0 mm/20.1-22.0 mm and a long duration of LE treatment were less likely to get ectopic pregnant compared with patients with 14.1-16.0 mm lead follicles and shorter LE treatment (OR: 0.142, 95% CI: 0.023-0.891, P =0.037; OR: 0.142, 95% CI: 0.022-0.903, P =0.039; OR: 0.445, 95% CI: 0.235-0.840, P = 0.013). Conclusions: The presence of a spontaneous LH surge in triggered LE-HMG IUI cycles does not appear to improve pregnancy rates. Thus, we suggest that waiting for an LH surge to occur is not necessary in triggered LE-HMG IUI cycles.

Nintedanib Treatment After Ovulation is an Effective Therapeutic Strategy for the Alleviation of Ovarian Hyperstimulation Syndrome (OHSS) in a Mouse Model.

PURPOSE: Ovarian hyperstimulation syndrome (OHSS) is a serious complication of controlled ovarian hyperstimulation. In this study, we hope to explore whether nintedanib, a tyrosine kinase inhibitor, can inhibit OHSS by blocking signaling of vascular endothelial growth factor in a mouse model. Considering that nintedanib been approved for the treatment of some diseases. We believe that nintedanib has important potential in the treatment of OHSS. METHODS: Female ICR mice aged 6-8 weeks with similar initial weights were used to establish the OHSS model. At 12 and 24 hours after human chorionic gonadotropin (hCG) trigger, we administered nintedanib by subcutaneous injection and analyzed the OHSS-related physiological characteristics and biochemical indices of the model mice within 48 hours after hCG-trigger. RESULTS: Nintedanib significantly alleviated the symptoms of OHSS after hCG-trigger compared with those of OHSS group (weight change, P < 0.0001; ovarian weight, P < 0.0001, peritoneal exudation level, P < 0.01). Further investigation proved that the corpus luteum (number, P < 0.001; diameter, P < 0.0001) and luteal vessel (P < 0.0001) development were inhibited in the nintedanib administration group. Then, the vascular permeability test showed that the capillary bleeding points (P < 0.0001) were also significantly reduced in nintedanib administration group. Gene expression tests demonstrated that the intercellular connection-related genes expression in the nintedanib administration group was similar to that in the no-OHSS induced group. Further detection of coagulation and thrombosis indices indicated that the nintedanib administration in the OHSS model did not increase the risk of thrombosis or bleeding. CONCLUSION: Our study demonstrated that nintedanib can alleviate and manage the symptoms of OHSS in a mouse model. These findings identify a feasible scheme for the prevention and treatment of OHSS in clinical practice in the future. Moreover, since the scheme can be implemented after ovulation, it will not cause potential adverse effects on gametogenesis, fertilization or embryonic development.

Using Data Science To Guide Aryl Bromide Substrate Scope Analysis in a Ni/Photoredox-Catalyzed Cross-Coupling with Acetals as Alcohol-Derived Radical Sources.

Ni/photoredox catalysis has emerged as a powerful platform for C(sp2)-C(sp3) bond formation. While many of these methods typically employ aryl bromides as the C(sp2) coupling partner, a variety of aliphatic radical sources have been investigated. In principle, these reactions enable access to the same product scaffolds, but it can be hard to discern which method to employ because nonstandardized sets of aryl bromides are used in scope evaluation. Herein, we report a Ni/photoredox-catalyzed (deutero)methylation and alkylation of aryl halides where benzaldehyde di(alkyl) acetals serve as alcohol-derived radical sources. Reaction development, mechanistic studies, and late-stage derivatization of a biologically relevant aryl chloride, fenofibrate, are presented. Then, we describe the integration of data science techniques, including DFT featurization, dimensionality reduction, and hierarchical clustering, to delineate a diverse and succinct collection of aryl bromides that is representative of the chemical space of the substrate class. By superimposing scope examples from published Ni/photoredox methods on this same chemical space, we identify areas of sparse coverage and high versus low average yields, enabling comparisons between prior art and this new method. Additionally, we demonstrate that the systematically selected scope of aryl bromides can be used to quantify population-wide reactivity trends and reveal sources of possible functional group incompatibility with supervised machine learning.

Phenotypic Heterogeneity and Fertility Potential of Patients With 17-Hydroxylase/17,20-lyase Deficiency.

CONTEXT: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) is caused by a human CYP17A1 gene mutation and has the classical phenotype of hypertension, hypokalemia, sexual infantilism, and primary amenorrhea in females (46,XX) and disorders of sexual development in males (46,XY). To date, few cases of 17OHD have been reported, and the likelihood of pregnancy has rarely been explored. OBJECTIVE: To study the clinical characteristics, phenotype heterogeneity, genotyping, and the likelihood of pregnancy of patients with 17OHD. DESIGN: Genotype analysis was performed by direct sequencing of the CYP17A1 gene and next-generation sequencing in nonclassical patients. In vitro enzyme activity assays and 3-dimensional structure observations were used to assess the function of 3 missense mutations of the CYP17A1 gene. Progestin-primed ovarian stimulation (PPOS) was chosen for ovulation induction in 2 patients. RESULTS: Eight mutations were identified from 13 patients, including the homozygous mutations p. N395D and p. R496C and compound heterozygous mutations p. Y329fs/p. A421A and p. I332T/p. D487_F489del in 4 nonclassical patients. For the 3 missense mutations, an in vitro functional study showed mild impairment of 17α-hydroxylase activities 15.3-25.0% but residual 17,20-lyase activities 6.6%-9.4%. Two 46,XX females succeeded in pregnancy and delivery by combined PPOS, in vitro fertilization embryo transfer (IVF-ET), and the use of low-dose glucocorticoids. CONCLUSIONS: Partial 17OHD present nonclassical clinical features, without hypertension and hypokalemia. Successful pregnancy in such 46,XX patients could be attained by the appropriate choice of ovulation induction regimen, precise dose of glucocorticoid to reduce progesterone levels, and the use of IVF-ET.

The Cycle Characteristics and Outcomes of Infertile Nonclassic 21-Hydroxylase Deficiency Patients Undergoing Ovarian Stimulation for In Vitro Fertilization.

BACKGROUND: The objective of the work was to investigate the cycle characteristics and outcomes of infertile women with nonclassic 21-hydroxylase deficiency (21-OHD) undergoing in vitro fertilization (IVF). METHODS: Twenty-five infertile nonclassic 21-OHD patients were retrospectively observed. From cycle day 3, patients were given human menopausal gonadotropin (HMG) 150 IU/d or 225 IU/d daily. Dexamethasone was administered orally at 0.75 mg/d. Ovulation was co-triggered by human chorionic gonadotropin (hCG) and triptorelin. Binary logistic regression was performed to quantify the effect of IVF parameters on embryo transfer cycle outcomes. The receiver operating characteristic (ROC) curve was used to determine cutoff points of the selected confounders for predicting pregnant probabilities. RESULTS: In controlled ovarian hyperstimulation (COH) cycles, there was a trend that the viable embryos group consisted of more polycystic ovary (PCO) patients. In embryo transfer (ET) cycles, differences were detected in the usage rate of dexamethasone and the minimum progesterone (P4) and total testosterone (TT) values between the non-pregnant group and the biochemical pregnant group. Binary logistic regression analysis confirmed that decreasing minimum P4 and body mass index (BMI) value was respectively correlated with increasing pregnancy probability. ROC analysis proved that the cutoff values for minimum P4 and BMI were 0.45 ng/ml and 23.36 kg/m2. CONCLUSION: In COH cycles, the ultrasonographic appearance of ovary helps to predict the number of viable embryos. In ET cycles, dexamethasone obviously improves the pregnancy rate. If the minimum P4 value before endometrial transformation cannot be kept below 0.45 ng/ml, we may consider cycle cancellation. Moreover, it is suggested that BMI of nonclassic 21-OHD women is regulated below 23.36 kg/m2.

The effects of low-dose human chorionic gonadotropin combined with human menopausal gonadotropin protocol on women with hypogonadotropic hypogonadism undergoing ovarian stimulation for in vitro fertilization.

OBJECTIVES: To investigate the effects of low-dose human chorionic gonadotropin (hCG) combined with human menopausal gonadotropin (HMG) protocol on cycle characteristics and outcomes of infertile women with hypogonadotropic hypogonadism (HH) undergoing ovarian stimulation for in vitro fertilization (IVF). DESIGN: A retrospective cohort study. SETTING: Tertiary-care academic medical centre. PATIENT(S): Forty-six infertile patients with HH and seventy-one infertile patients with tubal factor (TF) infertility undergoing IVF. INTERVENTION(S): In the study group, all 46 HH patients were given low-dose hCG (50-300IU/d) in combination with HMG daily from cycle day 3. Meanwhile, a control group consisting of 71 patients with tubal factor infertility was set up, where the infertile women were given triptorelin 3.75 mg on cycle day 3 for desensitization and started stimulation with HMG only 5 weeks later. Transvaginal ultrasound and serum sex steroids were used for monitoring the development of follicles. Ovulation was triggered by hCG 5000IU when dominant follicles matured. Viable embryos were transferred on the third day after ovum pickup or cryopreserved for later transfer. MAIN OUTCOME MEASURE(S): The primary outcome measure was the clinical pregnancy rate. Secondary outcomes included hCG day P4, ratio of E2/follicle count, number of oocytes retrieved, number of viable embryos, implantation rate, ongoing pregnancy rate and cumulative pregnancy rate. RESULT(S): With lower basal FSH, LH and E2, HH patients showed longer HMG stimulation duration (13 (10-22) d vs 12 (8-18) d, P < .001) and higher HMG dose (2960 ± 560 IU vs 2663 ± 538 IU, P = .005). Whilst the antral follicle count (AFC), number of follicles with diameters greater than 10mm on trigger day and oocytes retrieved were less in the HH group, the number of follicles with diameters greater than 14 mm and viable embryos were comparable. The ratio of E2/follicle count (>10 mm) and E2/follicle count (>14 mm) were distinctively higher in the HH group (1056 ± 281 vs 830 ± 245, P < .001; 1545 ± 570 vs 1312 ± 594pmol/L, P = .037; respectively). The clinical pregnancy rate, implantation rate, ongoing pregnancy rate and cumulative pregnancy rate per woman were comparable between the two groups. Comparison among the subgroups with different hCG dosage showed that HMG duration shortened with the increase of daily hCG dose (14.84 ± 2.88 vs 13.96 ± 2.63 vs 12.96 ± 1.30 days, P = .037). No significant differences were detected in outcomes between fresh embryo transfer (ET) group and frozen-thawed embryo transfer (FET) group. CONCLUSION(S): Low-dose hCG combined with HMG is a feasible protocol for HH women undergoing ovarian stimulation in IVF, providing favourable cycle characteristics and pregnancy rates. Low-dose hCG reduces HMG duration, whilst the hCG dose and embryo quality are not positively correlated. The outcomes of FET are comparable to ET, which provides a greater chance of success from IVF in the low responders with HH.

Clomiphene citrate is associated with favorable cycle characteristics but impaired outcomes of obese women with polycystic ovarian syndrome undergoing ovarian stimulation for in vitro fertilization.

The aim of this study was to explore the effect of clomiphene citrate (CC) on the cycle characteristics and outcomes of obese women with polycystic ovarian syndrome (PCOS) undergoing ovarian stimulation for in vitro fertilization (IVF).This is a retrospective cohort study, and it was conducted at the tertiary-care academic medical center.This study included 174 obese PCOS patients undergoing IVF.In the study group (n = 90), CC and human menopausal gonadotropin (HMG) were administered simultaneously beginning on cycle day 3, while in control group (n = 84) HMG was used only. Both of the 2 groups used medroxyprogesterone acetate (MPA) for preventing premature luteinizing hormone (LH) surges. Ovulation was cotriggered by a GnRH agonist and hCG when dominant follicles matured.The primary outcome measure was the number of oocytes retrieved. Secondary outcomes included the number of top-quality embryos, maturation rate, fertilization rate, cleavage rate, incidence of premature LH surge, and OHSS.The study group received obviously lower total HMG dose [1650 (975-4800) vs 2025 (1350-3300) IU, P = 2.038E-4] but similar HMG duration. While the antral follicle count (AFC) is higher in study group, the number of oocytes retrieved and top-quality embryos are remarkably less [5 (0-30) vs 13 (0-42), P = 6.333E-5; 2 (0-14) vs 3.5 (0-15), P = .003; respectively]. The mature oocyte rate is higher in study group (P = .036). No significant differences were detected in fertilization rate and cleavage rate between 2 groups.CC has a positive influence on cycle characteristics, but might be correlated with the impaired IVF outcomes (less oocytes retrieved and top quality embryos, lower oocyte retrieval rate) in obese PCOS patients undergoing IVF, when HMG and MPA are used simultaneously.