Relationship between pregnancy rate and number of intrauterine insemination cycles during the study of comparative efficacy of letrozole and clomiphene citrate adjuvants to gonadotropin stimulation in controlled ovarian stimulation cycles combined with intrauterine insemination therapy

Background: Infertility is commonly defined as the failure of conception after at least twelve months of unprotected intercourse. Factors contributing are both male and female in which unexplained etiology accounts for 51%, male factor 28%, endometriosis 17% and ovulatory disorders 4%.Methods: Prospective, randomized study was conducted at DRRPG medical college, Tanda, Kangra, Himachal Pradesh. In our study, patients were randomized into two groups of 30 each. Women in group A received clomiphene citrate 100mg/day and group B received letrozole 2.5 mg/day from day 3-7 of menstrual cycle. All the patients received human menopausal gonadotropin 75 U given every alternate day from day 5 until HCG administration. Ovulation was triggered with recombinant HCG (5000 IUIM) when the dominant follicles reached 18 mm in diameter. A single IUI was performed 36 hours later. A maximum of four cycles were given.Results: In our study, total number of induction cycles given in group A and B were 120 and 114 respectively. Out of these, 112 and 111 IUI cycles were done in group A and B respectively. A pregnancy rate of 1.66% and 7.87% per IUI cycle was observed in group A and B respectively.Thus it is concluded that the pregnancy rates were significantly higher in letrozole group (30%) in comparison to clomiphene citrate group (6.66%).Conclusions: Aromatase inhibitor letrozole appears to constitute a good alternative to clomiphene citrate in patients with unexplained infertility undergoing gonadotropin-stimulated COS cycles combined with IUI therapy.

The Study on Different Ovulation Induction Protocols used for Intrauterine Insemination and their Pregnancy Rate in Infertile Couples

Infertility affects millions of people of reproductive age worldwide and has an impact on their families and communities. Infertility is a disease of male or female reproductive system defined by failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse. Infertility is treated by different fertility drugs, ovulation induction (OI), intrauterine insemination (IUI) and in-vitro fertilization (IVF). The aim of the study is to find out the significant difference in pregnancy rate with different OI protocols used for IUI. OI is the first line treatment given to infertile women. In OI, medications are given to women for egg development and for release of eggs. OI is monitored by follicular study by ultrasonography. Semen is collected from the male partner and processed with culture media to retrieve high motile sperms, which are injected into the uterus of the female. A prospective randomized study was performed among 1343 IUI cycles. OI is started on Day 2 or Day 3 of the menstrual cycle. OI protocol is grouped according to the fertility drugs used for stimulation. The fertility drugs used for the stimulation are Clomiphene Citrate, Letrozole, Recombinant Gonadotropins, Human menopausal Gonadotropins (HMG), Human chorionic Gonadotropin (HCG). Group A uses Clomiphene citrate and HCG, Group B uses Clome, recombinant Gonadotropins and HCG. Group C uses Clome, Human menopausal Gonadotropin and HCG; Group D uses Letrozole and HCG. Group E uses Letrozole recombinant Gonadotropin and HCG. Group F used Letrozole, Human menopausal Gonadotropin and HCG. Group G used recombinant Gonadotropin and HCG. Group H used Human menopausal Gonadotropin and HCG. Group I uses only HCG. Group J was a natural cycle monitoring without any medication and was used as a control. Pregnancy rates were calculated for different age groups with different protocols. The result shows that Group B had 13% pregnancy, Group C had 9%, Group D had 3%, Group E had 10%, Group G had 11%, Group G had 11%, Group H had 7%, Group I had 4%, and Group J had 8% of pregnancy rate. The statistical analysis shows there is no significant difference with different stimulation protocols used.

Analysis of the clinical efficiency of human menopausal gonadotropins in the assisted reproductive technology program

Introduction. Comparative analysis of urinary and recombinant gonadotropins is ongoing to improve the efficiency of assisted reproductive technology programs. Particular interest focused on the identification of individual groups of patients with maximal efficacy of using certain ovarian stimulation drugs in an assisted reproductive technology program.Objective. To review the application of Menopur Multidose 1200 IU for ovarian stimulation in assisted reproductive technology protocols with gonadotropin-releasing hormone agonists (GnRH) or gonadotropin-releasing hormone antagonists (GnRH antagonists) in the current clinical practice.Materials and methods. The study retrospectively enrolled 4,080 women aged 20-43 years. Ovarian stimulation in the Assisted Reproductive Technology program was performed using the GnRH antagonist protocol in 65.8% of patients and the GnRH agonist protocol with Menopur Multidose 1200 IU with or without the additional Menopur 75 IU in 34.2% of women.Results. Clinical and laboratory data of the patients, stimulated cycle parameters, characteristics of the embryological stage, and results of the assisted reproductive technology program were analyzed. The frequency of obtaining degenerated oocytes did not exceed 5%. The relative number of blastocysts of good quality was 59.9%, while for patients in the older age group, the figure was 54.6. The average pregnancy rate in patients in the “Menopur Multidose 1200 IU p/k” group was 39.3%, which corresponds to high-performance indicators of the assisted reproductive technology program.Conclusions. Administration of highly purified human menopausal gonadotropin (hMG) (Menopur Multidose 1200 IU) to stimulate ovarian function in patients of different ages is accompanied by an adequate number of mature oocytes, good quality blastocysts, and satisfactory clinical pregnancy rates. Thus, highly purified human menopausal gonadotropin is not inferior to recombinant follicle-stimulating hormone(r-FSH) concerning the efficacy of assisted reproductive technology programs.

A novel heterozygous mutation of CHD7 gene in a Chinese patient with Kallmann syndrome: a case report

Background Variants of chromodomain helicase DNA binding protein 7 (CHD7) gene are commonly associated with Kallmann syndrome (KS) and account for 5–6% of idiopathic hypogonadotropic hypogonadism (IHH) cases. Here we report a novel mutation of CHD7 gene in a patient with KS, which may contribute to the better understanding of KS. Case presentation A 29-year-old male patient with KS and a chief complaint of delayed puberty for 13 years (Tanner B Stage< 4) was admitted to the Department of Endocrinology of the First Affiliated Hospital of Zhejiang University (Hangzhou, China) in September 2019. Dual-energy X-ray absorptiometry (DEXA) showed low bone density in both lumbar spine (L1 ~ L5 mean Z-score − 3.0) and femoral neck (Z-score − 2.7). Dynamic contrast-enhanced magnetic resonance imaging (MRI) of pituitary and contrast-enhanced computed tomography (CT) showed no abnormal findings. Ophthalmological evaluation showed that his both eyes showed exotropia, and no sight loss was noted. Heterozygous c.1619G > T mutation of TCD7 gene (p.G4856V) was detected, whereas none of his family members had this mutation. Human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) were injected for three times/week to treat idiopathic hypogonadotropic hypogonadism (IHH). After several months of therapy, the patient’s health condition improved. His testicles became larger, and his secondary sexual characteristics improved after treatment. Conclusion Exploration of the novel splice-site mutation of CHD7 may further our current understanding of KS.

AN INTERVENTIONAL STUDY OF LOW DOSE HUMAN MENOPAUSAL GONADOTROPIN WITH CLOMIPHENE CITRATE FOR OVULATION INDUCTION IN CLOMIPHENE RESISTANT POLYCYSTIC OVARIAN SYNDROME WOMEN IN THE DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY, SMS MEDICAL COLLEGE, JAIPUR

Background: Methods: The present study is a single arm interventional study done at a tertiary care hospital in a metropolitan city. The study participants were the females who had infertility due to PCOS and resistant to clomiphene citrate, and participants were given HMG in a sequential manner with Clomiphene citrate and ovulation was observed using the TVS. Results: 79% of the study participants ovulated at the end of the study as a final outcome and only 25 participants who constitute 21% of the total had not ovulated. No cases of ovarian hyperstimulation and multiple gestation was reported. Conclusion: The study thus concludes that CC with low dose HMG is an efficient and safe method for induction of ovulation in females with CC resistant PCOS related infertility without the dangers of OHSS and other adverse events, also the presence of normal BMI can help in a better rate of ovulation Keywords: HMG, TVS, Infertility

O-113 Effectiveness and treatment cost of assisted reproduction technology for women stimulated by gonadotropin in France: A cohort study using the National Health Database

Study question How effective is Assisted Reproduction Technology (ART) in terms of cumulative live birth rate (CLBR) in France, depending on the gonadotropin used? Summary answer Among 214,539 stimulations, originator follitropin-alfa was associated with significantly higher CLBR when compared to Highly Purified-Human Menopausal Gonadotropin (HP-HMG) and biosimilars. What is known already Deciding which type of gonadotropin to prescribe for a woman undergoing controlled ovarian stimulation (COS) remains difficult. The effectiveness of different gonadotropins is one factor to consider. However, studies comparing r-hFSH-alfa, its biosimilars and HP-HMG are scarce and are mostly based on a single ART treatment cycle and fresh embryo transfers. Some clinical trials have shown similar pregnancy, pregnancy loss, and live birth rates after fresh embryo transfer (ET) between HP-HMG and r-hFSH. However, because more oocytes are retrieved with r-hFSH when compared to HP-HMG, it is logical to hypothesize that the CLBR is higher with r-hFSH. Study design, size, duration A non-interventional study based on the French National Health System (SNDS) database was designed to assess the CLBR and treatment costs from the national payer perspective of four gonadotropin groups (originator follitropin-alfa (r-hFSH-alfa), its biosimilars, HP-HMG and r-hFSH-beta) used for COS cycles leading to oocyte pick-up (OPU) between 01/01/2013 and 31/12/2017 with a follow-up period up to 31/12/2018. The study compared CLBR, with originator r-hFSH-alfa as the reference. Participants/materials, setting, methods Women with COS cycles resulting in OPU with one of the specified gonadotropins were included. Data were extracted from billing and reimbursement records of outpatient healthcare consumption and national hospital discharge databases using a unique, anonymized patient number. CLBR was estimated using an Andersen–Gill model, adjusted for clinical baseline, stimulation and ET variables. Costs were reported as secondary outcomes. Main results and the role of chance 135,752 women (mean age 34.1), underwent 214,539 stimulations leading to OPU and contributed one (61.5%), two (24.8%), three (9.4%) or four (3.2%) COS cycles. COS cycles were stimulated with either Originator r-hFSH-alfa (46%), HP-HMG (29%), r-hFSH-beta (21%) or r-hFSH-alfa biosimilars (4%). Over the study period, CLBR reached 20.5%; 21.9% with originator r-hFSH-alfa, 17.9% with HP-HMG, 21.3% with r-hFSH-beta and 18.4% with r-hFSH-alfa biosimilars. After adjusting for age, pre-treatment, GnRH analog, ovulation triggering, luteal phase support, previous COS, fresh or frozen ET and type of center, as possible cofounding variables, the adjusted hazard ratio (HR) for CLBR (delivery [originator r-hFSH-alfa as reference]) was 0.88 (95% CI 0.86 to 0.95, p &lt; 0.0001) with HP-HMG; 0.98 (95% CI 0.95 to 1.00, p = 0.1020) with r-hFSH-beta, and 0.84 (95% CI 0.79 to 0.90, p &lt; 0.0001) with r-hFSH-alfa biosimilars. Although the mean acquisition cost of r-hFSH-alfa during the study was 33% higher than HP-HMG and 20% higher than r-hFSH-alfa biosimilars, the global ART management costs were only 4% higher than HP-HMG, 3% higher than r-hFSH-beta, and similar to r-hFSH-alfa biosimilars. Limitations, reasons for caution Patients were included only from oocyte pick-up, due to missing data in the SNDS database, meaning that it was not possible to estimate the proportion of cancelled cycles. Furthermore, as r-hFSH-alfa biosimilars were only available since 2015, results for biosimilars should be interpreted with caution. Wider implications of the findings This population-wide French study confirms other Real-World and meta-analysis evidence that CLBR is higher with originator r-hFSH-alfa than with HP-HMG or r-hFSH-alfa biosimilars, respectively, and are relevant for healthcare professionals to support gonadotropin treatment decision making. To further support this, the cost analysis should be completed by a cost-effectiveness analysis. Trial registration number Not applicable