New study results published in Human Reproduction could pave the way for an additional treatment option for the estimated 1.5 million women worldwide who undergo in vitro fertilization (IVF) treatment each year. In the Lotus I study, which involved more than 1,000 women across 38 international sites, oral dydrogesterone had similar efficacy and tolerability to micronized vaginal progesterone (MVP), which is the current standard of care globally to prepare the uterus lining for pregnancy.
IVF is one of several methods of assisted reproduction technology whereby a fertilized embryo is transferred to the woman’s uterusiv. Progesterone or a related hormone, such as dydrogesterone, is used in IVF to prepare the lining of the uterus (luteal phase support) to allow a fertilized egg to implant.
According to a 2015 analysis by Ernst & Young (EY), infertility has a high prevalence affecting nearly 10 – 15 per cent of married couples in India. Nearly 27.5 million couples who are actively seeking children suffer from infertility. Despite the increasing demand for infertility treatment in India, only one per cent of couples in India seek assisted reproductive treatment such as IVF.
MVP is the most commonly used method of administering progesterone in IVF centers globally, but is associated with side effects, such as irritation and discharge, as well as poor patient acceptance.
Lotus I, a phase III randomized controlled clinical studyix, evaluated the effects of oral dydrogesterone in luteal support in IVF. The findings of the Lotus I study provide clinical evidence for an oral treatment option. Besides its ease of administration, the Lotus I study concluded that oral dydrogesterone is similarly well-tolerated and efficacious compared to MVP.
In the Lotus I study, oral dydrogesterone achieved similar results to MVP in terms of the presence of fetal heart beats at 12 weeks gestation, representing an ongoing pregnancy. The two treatment groups also had similar pregnancy and live birth rates.
The results from the Lotus I study add to the body of evidence from smaller IVF studies of the benefits of using oral dydrogesterone for luteal support as part of IVF.
The Lotus I study achieved its primary efficacy endpoint, demonstrating non-inferiority of oral dydrogesterone versus MVP with the presence of fetal heartbeats at 12 weeks of gestation. Results were similar between the full analysis sample (FAS) and per protocol sample (PPS) for all measures of efficacy. In the PPS, the pregnancy rates at 12 weeks gestation were 37.6 per cent and 33.1 per cent in the oral dydrogesterone and MVP treatment groups, respectively, demonstrating non-inferiority of oral dydrogesterone to MVP. For the secondary objective, the Lotus I study demonstrated that pregnancy rate two weeks after embryo transfer and at eight weeks of gestation as well as live birth rates were similar for both treatments.
Lotus I was a double-blind, double-dummy, two arm multicenter, multinational phase III randomized controlled study conducted across 38 sites in Austria, Belgium, Germany, Finland, Israel, Russia and Spain. The study took place from August 2013 to March 2016 and was performed in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.
Lotus I participants were randomized to receive either oral dydrogesterone 10 mg or MVP 200 mg three times daily. This treatment to prepare the lining of the uterus (luteal support) was started on the day of oocyte retrieval (egg collection) and continued for up to 12 weeks of gestation.
Dydrogesterone has been marketed for more than 50 years for conditions related to progesterone insufficiency. The safety and tolerability profile of the drug has been well-established through the experience of an estimated 94 million patients globally.
The use of dydrogesterone is specific to each country regulatory approval and includes the treatment of threatened or recurrent miscarriage, as well as luteal phase support in infertility and menstrual disorders, endometriosis and hormone replacement therapy post menopausex.
Currently, dydrogesterone is not approved in any country for the treatment of luteal phase support in IVF or artificial reproductive technology.