Comparison Between Testosterone and Estradiol Over the Homogenization of Follicular Cohort
Comparison Between Testosterone and Estradiol Over the Homogenization of Follicular Cohort
In vitro fertilization(IVF) with Gonadotropin-releasing hormone (GnRH) antagonist is one of
 the most used protocol for the treatment of infertile couples nowadays. Despite several
 advantages over GnRH agonist, the antagonist may be associated with a slightly reduction in
 pregnancy rates.

 Several medications have been tested in order to increase ovarian response to ovulation
 induction, including estradiol and testosterone. A clinical trial in women with IVF
 indication will be performed and this women will be randomly assigned to receive topic
 testosterone, oral estradiol or no pre-treatment prior to IVF with human Chorionic
 Gonadotropin (hMG) and GnRH antagonist. The primary endpoint will be the size and number of
 follicles on the beginning of the cycle, after pre-treatment.
One of the key-words to a successful IVF it is the response to the ovarian controlled
 stimulation. Nowadays, one of the most common protocols includes exogenous gonadotropins and
 GnRH antagonist, followed by IVF. The GnRH antagonist avoids the premature peak of LH and has
 advantages in relation to the GnRH agonist; however it might have a negative effect over the
 pregnancy rate. One possible explanation is the heterogeneity of the follicular cohort at the
 moment of ovarian puncture, due to the rise of FSH at luteal-follicular transition. The
 estrogen can inhibits this rise of Follicle-Stimulating Hormone (FSH), resulting in a more
 synchronic cohort. Previous studies have demonstrated a reduction in the cancellation rates
 with estradiol in the luteal phase of the cycle prior to the beginning of IVF using GnRH
 antagonist protocol, with a trend towards better quality of transferred embryos and better
 implantation rates when compared to the standard protocol with antagonist. The use of
 androgens is based on the assumption that they generate an increase in FSH receptors in the
 granulosa cells, increase in follicular growth and estrogen production, according to animal
 and human studies. Despite promising initial results, further studies are needed to evaluate
 the benefit of testosterone as a pretreatment in women undergoing IVF.

 The study protocol is the following: Around the 20th day of the cycle prior to the choice of
 IVF, transvaginal pelvic ultrasound and serum progesterone dosage will be performed in all
 patients. After confirmation of ovulation and no contraindications for the continuation of
 the study, according to the randomization, testosterone gel, estradiol oral or no treatment
 will be initiated. Both medications will be continued until the first day of subsequent
 menstruation. After the menses, between the second and third day of the cycle, a new
 transvaginal ultrasound will be performed and blood tests will be collected for the dosage of
 FSH, Luteinizing Hormone (LH), progesterone and estradiol. On the same day, subcutaneous hMG
 (Menopur®) will be started at a dose between 150 and 300 IU / day, according to age and HAM,
 which will be subsequently adjusted according to the ovarian response on serial
 ultrasonography. When the largest follicle reaches a mean diameter of 14 mm, the GnRH
 antagonist (Orgalutran ®) will be initiated to prevent early LH peak, and monitored
 follicular growth with echography every 1-2 days. HCG will be administered at a dose of
 10,000 IU (Choriomon®) when three or more follicles reach a mean diameter of 17 mm. After
 36h, follicular puncture will be performed transvaginally, under general anesthesia. Embryo
 transfer will occur between the third and fifth day after in vitro fertilization. Luteal
 support will be given with administration of progesterone 600 mg / day vaginally, initiated
 after the transfer and maintained until the first trimester of pregnancy if it occurs. Serum
 beta-HCG measurement will be performed on the 12th day after transfer, for evaluation of
 pregnancy implantation. Clinical gestation will be considered when there is evidence of
 intrauterine embryo with cardiac beats present on the ultrasound, after 6 weeks of transfer
 of the embryo (s).
Inclusion Criteria:

 -  Regular cycles (between 25-34 days)

 -  In vitro fertilization indication for male cause, unexplained infertility or tubal
 factor

 -  Both ovaries

 -  Thyroid-stimulating hormone(TSH) < 2,5 mU/L

 -  Anti-Müllerian hormone (AMH) between 1-5 ng/ml

 -  Body Mass Index (BMI) < 30

 Exclusion Criteria:

 -  Ovarian surgery

 -  Endometriosis

 -  Endocrinology or metabolic disorder

 -  Polycystic ovary syndrome (PCOS)

 -  Poor Ovarian Response (according to Bologna criteria)