Dual suppression with oral contraceptives and gonadotrophin releasing-hormone agonists improves in-vitro fertilization outcome in high responder patients

Abstract

Certain patients have a tendency for high response to gonadotrophin therapy which is often not ameliorated with prior gonadotrophin-releasing hormone agonist (GnRHa) suppression. As a result, these patients are frequently cancelled and often experience ovarian hyperstimulation syndrome (OHSS) episodes during in-vitro fertilization (IVF)-embryo transfer cycles. Patients with polycystic ovarian syndrome (PCOS) have been noted to be particularly sensitive to exogenous gonadotrophin therapy. We have developed a protocol which is effective in improving IVF outcome in high responder patients, including those with PCOS. Oral contraceptive pills (OCP) are taken for 25 days followed by s.c. leuprolide acetate, 1 mg/day, which is overlapped with the final 5 days of oral contraceptive administration. Low-dose gonadotrophin stimulation is then initiated on the third day of withdrawal bleeding in the form of either human menopausal gonadotrophins or purified urinary follicle-stimulating hormone at a dosage of 150 IU/day. Over a 5 year period, we reviewed our experience utilizing this dual method of suppression in 99 cycles obtained in 73 high responder patients. There were only 13 cancellations prior to embryo transfer (13.1%). The clinical and ongoing pregnancy rates per initiated cycle were 46.5 and 40.4% respectively. Only eight patients experienced mild-moderate OHSS following treatment. For those patients who had undergone previous IVF-embryo transfer cycles at our centre, significant improvements were noted in oocyte fertilization rates, embryo implantation rates and clinical/ongoing pregnancy rates with this protocol. Hormonal analyses revealed that the chief mechanism may be through an improved luteinizing hormone/follicle-stimulating hormone ratio following dual suppression. An additional feature of this dual method of suppression is significantly lower serum androgen concentrations, particularly dehydroepiandrosterone sulphate.

Oral contraceptive pretreatment does not improve outcome in microdose gonadotrophin-releasing hormone agonist protocol among poor responder intracytoplasmic sperm injection patients

“…Similarly, Biljan et al [18] reported the advantage of OC pretreatment during the long standard protocol of GnRH-a administration. Damario et al [19] also revealed that dual suppression with oral contraceptives and gonadotrophin releasing-hormone agonists improves invitro fertilization outcome in high responders. All of the above mentioned studies evaluated OCs used in normo and/or high responder patients during long luteal protocol.…”

Pretreatment with Oral Contraceptive Pills Does Not Influence the Pregnancy Rate in the Long Leuprolide Acetate Protocol

“…Apart from the above-mentioned studies, available experience with leuprolide acetate and OCP is limited to studies evaluating hyperresponder [12] or poor responder [13,14] cohorts of women. Among high responder patients, premedication with an OCP might decrease the cancellation rate and increase both the clinical and ongoing pregnancy rates when compared with their previous IVF cycle without OCP pretreatment [12].…”

Application of GnRH antagonist in combination with clomiphene citrate and hMG for patients with exaggerated ovarian response in previous IVF/ICSI cycles

“…Marci et al [26] proposed a low-dose stimulation protocol (starting at 75 IU FSH, increased by 37.5 IU every 4 days) and they obtained a high implantation (21.8%) and pregnancy (38.4%) rates without cycle cancellation. Damario et al [27] proposed dual suppression with oral contraceptives and GnRHa, and 150 IU gonadotropin was initiated from day 3. Although a 46.5% pregnancy rate was achieved, 13 cycles (13.1%) were cancelled before embryo transfer.…”