Luteinizing Hormone/Human Chorionic Gonadotropin Receptor N312S Single-Nucleotide Polymorphism and Its Impact on Clinical and Reproductive Outcomes in Assisted Reproductive Technology: A Prospective Cohort Study.

Objective The aim of this study was to determine the genotypic distribution of luteinizing hormone/human chorionic gonadotropin receptor (LHCGR) N312S single-nucleotide polymorphism (SNP) and to investigate its impact on clinical and reproductive outcomes in infertile Indian women undergoing assisted reproductive technology (ART). Study design and settings This was a prospective cohort study conducted at a tertiary care university hospital. Subjects and methods Infertile women aged between 21 and 40 years undergoing ART with an antagonist protocol were enrolled in this study. A 2-ml sample of peripheral venous blood was collected from each woman and genotyped for the LHCGR N312S SNP. Participants were divided into three groups based on their SNP: NN, NS, and SS. All subjects underwent controlled ovarian hyperstimulation (COH) through a gonadotropin-releasing hormone (GnRH) antagonist protocol and intracytoplasmic sperm injection (ICSI). Of the 140 women recruited based on selection criteria, 128 underwent embryo transfer. We compared the genotypic distribution of the LHCGR N312S SNP, baseline characteristics, clinical outcomes, and reproductive outcomes in ART among the three groups. Data were analyzed using IBM SPSS Statistics for Windows, Version 29 (Released 2022; IBM Corp., Armonk, New York, United States). The chi-square test and Fisher-Irwin test were employed to evaluate significant differences among the qualitative categorical variables. A p-value of less than 0.05 was considered statistically significant. Results Among the test subjects, 19.3% were homozygous for the LHCGR N312 SNP (NN group), 38.6% were heterozygous (NS group), and 42.1% were homozygous for the LHCGR S312 SNP (SS group). Baseline characteristics were similar among the three groups. In terms of ovarian reserve tests, significantly lower anti-Müllerian hormone (AMH) levels were observed in the SS group compared to the NS and NN groups (2.8 ± 2.1 vs. 3.2 ± 2.5 vs. 4.3 ± 3.3; p=0.03). No significant differences were observed in COH outcomes such as duration of stimulation, total gonadotropin requirement, oocyte yield, or the number of good-quality embryos among the three groups. The cumulative pregnancy rate (82.9% vs. 50.0% vs. 38.2%, p=0.0005), cumulative clinical pregnancy rate (78.8% vs. 44.7% vs. 34.5%, p = 0.0005), and cumulative live birth rate (50.0% vs. 20.2% vs. 20.0%, p=0.005) were significantly higher in the NN group than in the NS and SS groups. Conclusion The study's findings suggest that LHCGR N312 may help predict reproductive outcomes in ART, which may aid in providing better counseling to infertile couples. We need more studies on individualized/personalized COH using pharmacogenomics for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) supplementation based on combined FSH and LH receptor SNP and to assess their effects on ART outcomes.

Exophytic Subserosal Uterine Adenomyomatous Polyp Mimicking Malignancy: A Case Report.

The epidemiological profile of adenomyosis has drastically changed in recent years due to advancements in imaging techniques. Even though adenomyosis is not uncommon in women of childbearing age, we present an intriguing case of a 30-year-old woman with long-standing progressive dysmenorrhea and infertility who had a posterior wall exophytic adenomyomatous polyp with full-thickness pseudo-invasion out of the uterine serosa into the right ovarian endometriotic cyst, mimicking malignancy. After surgical excision, the patient spontaneously conceived and delivered a live-term baby, soon after which she experienced an early recurrence. Clinicians must be aware of the distinctive features of different subtypes of adenomyosis to plan treatment and avoid invasive surgery.

Dual extrauterine ectopic pregnancy: double management.

A 30-year-old nulliparous woman was referred with suspected left ovarian ectopic pregnancy. She had undergone laparoscopic left salpingectomy for ruptured tubal ectopic pregnancy 3 weeks earlier, following treatment with medications for ovulation induction. Sonological examination revealed a left ovarian ectopic pregnancy corresponding to 8 0/7 weeks with cardiac activity. She underwent ultrasound-guided intrasac therapy with intrasac instillation of 3 mEq of potassium chloride followed by 50 mg of methotrexate. She was followed with weekly measurements of serum beta human Chorionic Gonadotropin (hCG) which returned to baseline after 65 days of the intrasac therapy. This case not only highlights the need for continued follow-up of the serum beta hCG after definitive management of an ectopic pregnancy in cases with multiple ovulations, but also the option of medical management in cases of advanced ovarian ectopic pregnancy. It also accentuates the necessity for adequate counselling to avoid conception in a multiple ovulation cycle.

Exclusive use of intrasac potassium chloride and methotrexate for treating cesarean scar pregnancy: effectiveness and subsequent fecundity.

STUDY QUESTION: Is exclusive use of intragestational sac potassium chloride (KCl) and methotrexate (MTX) effective in the management of viable cesarean scar pregnancy (CSP)? SUMMARY ANSWER: Exclusive use of intragestational sac KCl and MTX was effective in the management of viable CSP. WHAT IS KNOWN ALREADY: Owing to a paucity of randomized studies on management of CSP, evidence-based management remains unclear. Intragestational sac KCl or MTX along with either systemic MTX or surgical intervention, such as uterine artery embolization or dilation and curettage, has proved to be effective in the management of CSP. Furthermore, there are limited data in the literature on the use of exclusive intragestational sac KCl and MTX for management of CSP and subsequent fecundity. STUDY DESIGN SIZE DURATION: A prospective cohort study was conducted from June 2017 to September 2019. We recruited nine CSP patients referred to our unit. There was no lost to follow-up noted. PARTICIPANTS/MATERIALS SETTING METHODS: Patients with an ultrasound diagnosis of CSP who fulfilled the inclusion criteria were recruited. The study was conducted in a tertiary care center. Clinical symptoms, pregnancy viability, gestational age and human chorionic gonadotrophin (HCG) values determined the management in each individual case. Accordingly, patients were grouped into the expectant management (Group I, n = 3) and intragestational sac KCl with MTX (Group II, n = 6) groups. Demographic details, clinical characteristics, ultrasound details at diagnosis, post-treatment HCG normalization time, menses resumption, mass resolution and subsequent fecundity were noted. Descriptive statistics were used for analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Of the nine patients with CSP, six patients had viable CSP and required intervention. Out of these, four patients expressed a desire for future fertility. Mean gestational age at treatment among patients in Group II was 54.33 ± 7.51 days (range 46-65). Mean HCG value at the time of diagnosis was 84 110 ± 38 679.39 IU/l in Group II patients as compared with 2512 ± 709.36 in Group I. HCG had decreased by 92.7 ± 3.78% 2 weeks after intervention and normalized (<5 IU/l) by 53.5 ± 14.97 days. No major complications occurred and additional treatment was not required in these patients. Menstruation had resumed by 26 ± 6.6 days after treatment in Group II. On follow up, a small unresolved mass was present in two patients and the cesarean scar niche was visible in the remaining four patients. Out of the four patients desirous of future conception, three conceived naturally and one delivered a term baby via repeat lower segment cesarean section. LIMITATIONS REASONS FOR CAUTION: The main limitation of our study was small sample size. All the patients were asymptomatic at presentation and hence we cannot comment on use of this method in those presenting with active vaginal bleeding. WIDER IMPLICATIONS OF THE FINDINGS: Intragestational sac KCl plus MTX may be a highly effective approach for the management of viable CSP despite high initial HCG values. There seems to be no need for any further intervention. It can be considered as the first line minimally invasive treatment option in patients desirous of future fertility. Nevertheless, accumulation of further cases is required to validate this treatment modality. STUDY FUNDING/COMPETING INTERESTS: No specific funding was received to undertake this study. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

The Effect of Sperm DNA Fragmentation Index on the Outcome of Intrauterine Insemination and Intracytoplasmic Sperm Injection.

CONTEXT: Elevated sperm DNA fragmentation index (DFI) is found to affect normal embryonic development, implantation and fetal development after intrauterine insemination (IUI), in vitro fertilization and intracytoplasmic sperm injection (ICSI). Estimation of DFI by terminal deoxynucleotidyl transferase-mediated fluorescent deoxy uridine nucleotide nick end labeling (TUNEL) assay was found to have a high predictive value for pregnancy after fertility treatments. AIM: This study aims to find the effect of increased sperm DNA fragmentation by TUNEL assay on reproductive outcome after IUI and ICSI. PRIMARY OBJECTIVE: To find the association of DFI and pregnancy rate in IUI and ICSI. SECONDARY OBJECTIVES: To find the association of DFI with fertilization and implantation in ICSI. To find the association of DFI with miscarriage rate. SETTINGS AND DESIGN: A prospective observational study performed at a tertiary care university teaching hospital. SUBJECTS AND METHODS: 105 male partners of infertile couple planned for IUI and ICSI underwent estimation of sperm-DFI by TUNEL assay. The treatment outcomes were compared between the DFI-positive (≥20%) and DFI-negative (<20%) groups. STATISTICAL ANALYSIS USED: Statistical analysis was performed by SPSS version 17, Software. P < 0.05 was considered statistically significant. RESULTS: The men with abnormal semen analysis were significantly higher in the DFI-positive group (77.15% vs. 22.85%). There was no significant difference in the pregnancy rate in IUI cycles (17.6% vs. 11.8%); but in the ICSI, the pregnancy rate was significantly reduced in the DFI-positive group (16.7% vs. 47.4%). CONCLUSIONS: Elevated DFI significantly affects the pregnancy rate in ICSI cycles.

Does Pretrigger Echogenic Endometrium in Assisted Reproductive Technology Cycles Reflect Raised Serum Progesterone Level?

BACKGROUND: Serum progesterone is the main hormone of the luteal phase. The hyperechoic pattern of the endometrium in the luteal phase is believed to be induced by raised serum progesterone. Serum progesterone is found to be raised cases of controlled ovarian stimulation (COS) cycle on the day of ovulation trigger. AIM: This study aims to find the association between echogenicity of endometrium and raised serum progesterone. OBJECTIVE: The objective of this study is to determine whether raised pretrigger serum progesterone influences the echogenicity of the endometrium. MATERIALS AND METHODS: In this prospective observational study, we evaluated 221 patients who underwent COS. Echogenic patterns of the endometrium on transvaginal sonography were described as hypoechoic/trilaminar endometrium (Type A), isoechoic (Type B), and hyperechoic (Type C). The endometrial pattern and serum progesterone levels were evaluated on the day of ovulation trigger and value of ≥1 ng/ml was considered as elevated. RESULTS: A total of 168 patients out of 221 patients (76.01%) had elevated serum progesterone levels on the day of ovulation trigger. Type A endometrium was found in a total of 174 patients, of these 132 patients (75.86%) had raised serum progesterone. Type B endometrium was found in 35 patients, of these 27 patients (77.14%) had raised serum progesterone. Type C endometrium was seen in 12 patients, out of these 9 patients (75.00%) had raised serum progesterone level. There was no statistically significant difference in the echogenic patterns of endometrium in patients with raised progesterone (≥1 ng/ml). On intergroup comparison, the difference in the progesterone levels between type A and type C was statistically significant (P = 0.02), and on receiver operating characteristic curve analysis, echogenic endometrium was found to predict progesterone level of 1.57 ng/ml with a sensitivity of 58.3% and specificity of 58.4% only. CONCLUSION: Echogenicity of the endometrium does not reliably predict raised serum progesterone on the day of ovulation trigger.

Effect of Metformin-sustained Release Therapy on Low-density Lipoprotein Size and Adiponectin in the South Indian Women with Polycystic Ovary Syndrome.

OBJECTIVES: The aim of the study is to compare surrogate markers of cardiovascular disease (CVD) risk, such as adiponectin (APN) levels and low-density lipoprotein (LDL) size, before and after sustained release metformin (Met-SR) therapy in women with polycystic ovarian syndrome (PCOS). METHODS: Sixty women with PCOS and sixty age-matched controls in the age group 18-45 years were recruited after obtaining informed consent. Women with PCOS were initiated on Met-SR 1 g orally, which was increased to 1.5 g after 2 weeks and continued up to 24 weeks. Demographic data along with family history of type 2 diabetes mellitus, PCOS, and CVD were collected. Lipid profile plasma APN levels and LDL size were measured before and after therapy in the PCOS group. Data analysis was performed using the GraphPad Prism-5 software. RESULTS: Women with PCOS had greater dyslipidemia, lower APN level and LDL size, and increased lipid accumulating product index as compared to controls. After 6 months of Met-SR therapy, women with PCOS demonstrated significant increase in plasma APN levels and LDL size and significant decrease in weight, waist-hip ratio (WHR), waist circumference (WC), and blood pressure (BP). A significant decrease was observed in body mass index (BMI) in the overweight and obese PCOS subgroups. CONCLUSION: Met-SR increases LDL size, APN concentration and decreases weight, WC, WHR, and BP in patients with PCOS. Met-SR may have salutary effects on LDL particle size through effects on APN levels in women with PCOS.

Correlation of serum estradiol level on the day of ovulation trigger with the reproductive outcome of intracytoplasmic sperm injection.

BACKGROUND: Serum estradiol (E2) levels are measured in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), to assess the ovarian response and to predict ovarian hyperstimulation syndrome. The impact of peak E2 levels on IVF-ICSI outcome was found to be inconsistent in the previous studies. AIM: To evaluate the impact of the serum E2 levels on the day of ovulation trigger with the reproductive outcome of ICSI. SETTINGS AND DESIGN: Retrospective observational study. ART Center, at a Tertiary Care University Teaching Hospital. SUBJECTS AND METHODS: Eighty-nine infertile women, who underwent ICSI with fresh embryo transfer over a period of 3 years, were included in the study. The study subjects were grouped based on the serum E2 level on the day of ovulation trigger:- Group I - <1000 pg/ml, Group II - 1000-2000 pg/ml, Group III - 2000.1-3000 pg/ml, Group IV - 3000.1-4000 pg/ml, and Group V >4000 pg/ml. The baseline characteristics and controlled ovarian hyperstimulation (COH) outcome were compared among the study groups. STATISTICAL ANALYSIS USED: Chi-square test, Student's t-test, ANOVA, and logistic regression analysis. RESULTS: The study groups were comparable with regard to age, body mass index, ovarian reserve. Group V had significantly higher number of oocytes retrieved than I and II (18.90 vs. 11.36 and 11.33; P = 0.009). Group IV showed significantly higher fertilization rate than I, III, and V; (92.23 vs. 77.43, 75.52, 75.73; P = 0.028). There were no significant differences in the implantation rates (P = 0.368) and pregnancy rates (P = 0.368). CONCLUSION: Higher E2 levels on the day of ovulation trigger would predict increased oocyte yield after COH. E2 levels in the range of 3000-4000 pg/ml would probably predict increased fertilization and pregnancies in ICSI cycles.

Pregnancy outcome of assisted reproductive technology cycle in patients with hypogonadotropic hypogonadism.

CONTEXT: Ovulation induction in patients with hypogonadotropic hypogonadism (HH) is a challenge to the treating physician. The threshold for ovarian response in HH may differ substantially from that of normal patients. To reach that threshold levels of follicle stimulating hormone, in a step-up protocol longer duration of stimulation is required in some cases so as to prevent multiple pregnancy and to eliminate the risk of ovarian hyperstimulation syndrome. AIM: To evaluate the duration of stimulation, quality of oocytes, and embryo, and the pregnancy outcome in the assisted reproductive technology (ART) cycles in patients with HH. MATERIALS AND METHODS: Over the period of 4 years, we had 14 patients with HH in whom 21 cycles of ovulation induction were done. Of these 7 patients underwent oocyte retrieval and intracytoplasmic sperm injection (ICSI). We present a retrospective study of these 7 patients who underwent ART to evaluate the duration of stimulation, quality of oocytes and embryo, and the pregnancy outcome. RESULTS: In the study group on ovulation induction with gonadotropins, only one patient had the duration of stimulation of the standard 12 days, the remaining 6 patients took ≥12 days to respond to stimulation (maxium being 54 days). Mean ET in these patients was 8.9 mm. Six patients had >70% good quality MII oocytes. One patient responded poorly and had only 2 good quality MII oocytes (50%). After ICSI procedure, resultant embryos were of grade 1 and 2 in all the patients irrespective of the duration of stimulation. Fertilization rate in these patients was 85% (except in one 50% fertilization rate), and the cumulative pregnancy rate was 68.6%. CONCLUSION: In the patients with HH the quality of oocytes and embryos, and the pregnancy rate is not affected even if the duration of stimulation is prolonged.