Clomiphene Citrate plus Modified GnRH Antagonist Protocol for Women with Poor Ovarian Response Undergoing ICSI Treatment Cycles: Randomized Controlled Trial

Abstract

Objective: To compare Clomiphene Citrate (CC) and lower dose of Human chorionic Gonadotropins (HMG) plus Gonadotropins Releasing Hormone (GnRH) antagonist with conventional mid-luteal long agonist GnRH with higher dose of HMG in women with poor ovarian response, undergoing Intracytoplasmic Sperm Injection (ICSI). Poor ovarian response was defined as the development of less than 3 follicles ≥ 17 mm on HCG day in a previous midluteal GnRH agonist-IVF/ICSI cycle or women with age >35 years old.Method: Pilot non blind two arms parallel randomised controlled. Seventy women with a history of previous poor ovarian response undergoing controlled ovarian hyperstimulation (COH) for ICSI. Interventions: The control group (n=35) received a conventional mid-luteal long GnRH agonist treatment with daily injections of HP HMG, starting on day 2 of the cycle at a dose of 300 IU /day. In the study group (n=35), pre-treatment with luteal E2 supplementation was administrated followed by clomiphene citrate for 5 days, starting on day 2 of the cycle followed by daily injections of 225 IU HP HMG and GnRH antagonist from cycle day 6 onward. Results:There was no evidence of statistically significant difference between both groups regarding the clinical pregnancy rate per women randomized (5/35 (14%) versus 3/35 (9%); 95% CI: 0.39-8.09, p=0.43). The cost of ovarian stimulation per cycle worked out to be USD 208, 8 and 557.3 for CC ovarian stimulation group and conventional ovarian stimulation group respectively.Conclusion: CC and a lower dose of HMG plus GnRH antagonist preceded by mid-luteal E2 supplementation is as effective as the conventional ovarian stimulation in producing similar ICSI outcomes at lower cost in women with poor ovarian response.

Effectiveness of corifollitropin alfa used for ovarian stimulation of poor responder patients

“…Several ovarian stimulation approaches have been implemented with the aim to improve ovarian response and clinical outcome in poor responder women, but the results are still low and are often controversial. 11 – 21 The main reason for this controversy is due to the difficulties in establishing a uniform definition of poor responder patients, which can be universally applied. 34 Recently, the European Society of Human Reproduction and Embryology working group on POR has published a consensus paper describing three criteria to be used to identify women with POR, the so-called “Bologna Criteria”.…”

“…Several ovarian stimulation regimens have been used to treat poor responder women, but the results achieved are still controversial. These protocols include: varying the dose of gonadotropins or the day of menstrual cycle to initiate the stimulation, 11 , 12 high dose of gonadotropins in a gonadotropin-releasing hormone (GnRH) long protocol, 13 , 14 administration of GnRH and gonadotropins together in the follicular phase (flare-up protocol), 15 , 16 pre-cycle estrogen treatment, 17 growth hormone co-treatment, 18 gonadotropin suppression with oral contraception before IVF cycle, 19 using clomiphene citrate for stimulation 20 or clomiphene citrate with human menopausal gonadotropin in an antagonist GnRH protocol, 21 and non-stimulated (nature cycle) IVF treatment. 22 All these stimulation regimens have been used with a limited success, and adequate number and quality of retrieved oocytes in poor responder women still remain the most challenging items in assisted reproductive technologies.…”