None listed
Conditions
Brief summary
Despite the advances in assisted reproduction techniques, suboptimal In Vitro Fertilization(IVF) outcomes in women with Poor Ovarian Response(POR) still remains a challenge. Older women seeking IVF have suboptimal utcomes, at least partly due to inadequate number of eggs on conventional stimulation. This suboptimal response relates mainly to inadequate ovarian response but there is often also reduced live birth rates, increased risk cycle cancellation and a need larger doses of gonadotrophins, which increases both cost and risk of ovarian hyperstimulation syndrome (OHSS) risk. There is now growing evidence that androgens (or male hormones) may improve egg quality and numbers in women with POR. So far the androgens used in women with POR include testosterone and the pro-androgen hormone Dehydroepiandrosterone(DHEA) as well as aromatase inhibitor drugs, which increase the body’s own testosterone levels by blocking its conversion to estradiol. For each of these drugs, their multiple levels of action mean that it is not clear whether they produce any benefits by acting as an androgen (or male hormone). For this reason, this study is using dihydrotestosterone (DHT), the natural product of testosterone in the body of men and women, and which acts only as a pure androgen in the body. As a result, the study will determine for the first time whether these drugs do work as androgens or not and may refine and improve the treatment for POR. In this study we will temporarily increase the circulating levels of DHT during the time when oocyte (egg) development and maturation is occurring. This will be achieved by applying the DHT gel onto the skin once a day for 21 days prior to the start of IVF ovarian stimulation. Aims: To investigate the efficacy of DHT gel treatment applied onto the skin before an IVF stimulation cycle in women with poor ovarian response. Research Hypothesis DHT pre-treatment prior to an IVF cycle will improve the number of healthy, fertilisable eggs retrieved.
Interventions
DHT gel 5mg daily transdermal application for 21 days prior to controlled ovarian stimulation: The DHT or placebo gel will be similar and packed into capped 1 ml tuberculin-type syringes without needles and labelled with study and participant IDs. Each syringe has sufficient gel for 5 daily doses. Participating women will be given a supply of 5 syringes at the enrollment visit.. They will return the syringes at the end of the DHT treatment period (Day 21 of this study).
Compliance:
Compliance w
DHT gel 5mg daily transdermal application for 21 days prior to controlled ovarian stimulation: The DHT or placebo gel will be similar and packed into capped 1 ml tuberculin-type syringes without needles and labelled with study and participant IDs. Each syringe has sufficient gel for 5 daily doses. Participating women will be given a supply of 5 syringes at the enrollment visit.. They will return the syringes at the end of the DHT treatment period (Day 21 of this study). Compliance: Compliance will be determined by counting returned syringes on day 21. In addition women will provide at least one finger prick dried blood sample (DBS) at home to evaluate serum DHT during treatment. This uses our established DBS technology using a finger prick, similar to home blood glucose motoring, at home. Using a standard lancet, whole blood is dropped or smeared onto Guthrie-type filter paper and air dried. The filter paper with DBS can be kept in a dry place (plastic bag) at home without any special handling procedures unlike serum from venepuncture (i.e. no requirement for blood clotting, separation or refrigeration). The filter papers are returned with the used syringes for subsequently measurement of serum DHT.
Sponsors
Prof.David Handelsman
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
*Age >18 years *Modified Bologna criteria stratified by age -For women >40 years, no additional inclusion criteria -For women <40 years, at least one additional inclusion criterion either previous IVF cycle with POR (<3 oocytes with conventional stimulation) and/or impaired ovarian reserve (ultrasonic antral follicle count <7 follicles or serum AMH <1.1 ng/ml)
Exclusion criteria
*Use of androgens or pro-androgens in previous 2 months *Perimenopausal (no regular cycle, high serum FSH) *Major uterine abnormalities *History of untreated systemic medical disease or organ failure (eg impaired cardiac, respiratory, hepatic, or renal function) *Extensive skin disease that would interfere with use of the transdermal gel *Participation in other clinical trials of medical therapy
Outcome results
None listed