A Study of Comparison of Effectiveness of Letrozole (5mg) Versus Clomiphene Citrate (100 Mg) by Using Injection Human Placental Extract (HPE) for Ovulation Induction among Infertile Women

Abstract

Aim & Objective: To compare the efficacy of letrozole and clomiphene citrate (CC) by using injection of Human placental extract (HPE) for ovulation induction in infertile women. Introduction: Human placental extract (HPE) is a product of aqueous extraction from the biochemically enriched fresh human placenta which contains nucleotides, amino acids, peptides and vitamins in natural form. It is available as 2 ml ampule. Each ml. is derived from 0.1 gm. of fresh human placenta. Injection of HPE is used in infertility treatment for its anti-inflammatory property, due to which tubal inflammation is decreased and tubal motility increases which is useful for fertility. This is the hypothetical theory behind use of Injection of HPE for infertility treatment in infertile women. Clomiphene citrate has been traditionally used as drug of the choice for treatment of women with infertility. In the last decade, an aromatase inhibitor, letrozole has emerged as an alternative ovulation induction (OI) agent in anovulatory women with polycystic ovarian syndrome. Letrozole has a definitive role in anovulatory women who have not responded to clomiphene citrate therapy and this is confirmed by literatures. Background: Anovulatory dysfunction is a common problem and is responsible for about 40% of female infertility and among causes; PCOS (polycystic ovarian syndrome) is the leading cause. HPE is a product of aqueous extraction from the biochemically enriched fresh human placenta which contains nucleotides, amino acids, peptides and vitamins in natural form. HPE injection- properties: • Specific anti – inflammatory • Tissue repair–wound healing • Immunomodulatory • Melanopoetic • Debridement action It is useful in ovulation induction among infertile women who are infertile due to pelvic inflammatory disease (PID) or due to polycystic ovary syndrome (PCOS) because of its anti-inflammatory property which leads to reduction in tubal inflammation and increased tubal motility. Clomiphene citrate is considered as the first line of treatment for anovulatory dysfunction for a various reason, however Clomiphene citrate has some drawbacks like multi-follicular ovulation and Peripheral anti-estrogenic effect are areas of concern and desire for an effective alternative is need of the hour. An aromatase inhibitor, letrozole, was introduced into infertility practice in the year 2000 and is regarded as a second line option, particularly in women with clomiphene resistance and it has found acceptance in various clinical situations and the indications for its use have expanded. Design: Randomized double blind study. Setting: Scientific Research Institute, Surendranagar, Gujarat, India and a private practice setting. Patients & Methods: The study included 100 women who presented with infertility and were having polycystic ovary syndrome (PCOS). The study participants were divided into 2 groups of 50 each. With these injections, 1 group was given clomiphene citrate (100 mg daily) and another group was given; letrozole (5 mg daily), started from day 3 to day 5 of the menstruation cycle and continued up to 5 consecutive days. Both the groups have received Estradiol Valerate 4 mg. on the 12th day of menstruation until 16th day of menstruation; with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. Selected participants were of age between 20 to 39 years, had normal uterine cavity and had intercourse with male partner with a sperm concentration of at least 14 million per millilitre; and during the study the women and their partners agreed to have regular periodical intercourse with the intent of successful conception. The live birth of baby during the treatment period was the primary outcome. Second Outcome Measures: Follicular growth, endometrial thickness, pregnancy outcome. Results: Women who received Letrozole had more cumulative live births than those women who had received Clomiphene Citrate, (38 out of 50 [76%] vs. 29 out of 50 [58%]) after giving Injection of HPE with these ovulation induction drugs, without significant differences in overall congenital anomalies, with letrozole, as compared to clomiphene, the cumulative ovulation rate was higher. Clomiphene was associated with more numbers of episodes of hot flushes while letrozole was associated with fatigue and dizziness. Rates of other adverse effects were almost similar between these 2 groups. A significant difference in the follicular and endometrial development was evident between these 2 groups. Conclusion: Treatment with Injection of HPE with 2 ovulation induction drugs, Letrozole & Clomiphene Citrate - as compared to clomiphene, letrozole - an aromatase inhibitor, was associated with higher live-birth and ovulation rates in infertile women. The results of the study demonstrated that letrozole is non inferior to clomiphene citrate in the maintenance of endometrial thickness.