Luteal GnRH Agonist Research Articles

Achievement of pregnancy three times in the same patient during luteal GnRH agonist administration

Gonadotrophin-releasing hormone agonist (GnRHa) administration from the mid-luteal phase onwards is considered the gold standard of ovarian stimulation for IVF treatment. It might, however, coincide with an implanting spontaneous pregnancy. Concerns have therefore been raised with regard to the evolution of the resulting pregnancies and long-term outcome of the children born. The current case report describes the achievement of three pregnancies in the same patient during luteal administration of GnRHa. One pregnancy ended in spontaneous abortion and the other two resulted in the delivery of two female infants. The children have so far been followed for 3.5 and 7 years. The physical examination of both children was unremarkable. However, the older child has recently been diagnosed with attention deficit hyperactivity disorder and dyslexia.

Clinical management of low ovarian response to stimulation for IVF: a systematic review.

Poor response is not a rare occurrence in ovarian stimulation. Although not fully accepted, the most dominant criteria for poor ovarian response are small numbers of follicles developed or oocytes retrieved, and low estradiol (E2) levels after the use of a standard stimulation protocol. There is no ideal predictive test as the poor responder is revealed only during ovulation induction; however, increased levels of day 3 FSH and E2 as well as decreased levels of inhibin B can be used to assess ovarian reserve. Several protocols have been proposed for clinical management of low ovarian response in IVF. Although high doses of gonadotrophins have been used by the vast majority of authors, results have been controversial and prospective randomized studies have shown little or no benefit. The few available relevant studies do not indicate that recombinant FSH improves outcome. Flare-up GnRH agonist protocols (including all dosage varieties) produce better results than standard long luteal protocols. Luteal initiation GnRH agonist 'stop' protocols were shown to improve ovarian response according to prospective studies with historical controls, but this was not confirmed by well-designed prospective, randomized, controlled studies. The few available data obtained with GnRH antagonists have not shown any benefits. Adjuvant therapy with growth hormone (GH) or GH-releasing factors results in no significant improvement. The use of corticosteroids reduces the incidence of poor ovarian response in women undergoing IVF treatment. The limited data obtained with nitric oxide donors are encouraging. Pretreatment with combined oral contraceptives prior to stimulation may help ovarian response. No benefit was observed with standard use of ICSI or assisted hatching of zona pellucida. Finally, natural cycle IVF has produced results which are comparable with those obtained with stimulated cycles in true poor responders. Well-designed, large-scale, randomized, controlled trials are needed to assess the efficacy of these different management strategies.

Delaying the initiation of progesterone supplementation results in decreased pregnancy rates following in vitro fertilization: a randomized, prospective study.

Objective: To compare in vitro fertilization outcome between two protocols for luteal phase progesterone supplementation: one beginning on day 3 following retrieval and the other beginning on day 6 following retrieval. Design: Prospective, randomized study. Materials/Methods: 126 consecutive patients undergoing IVF at our institution between January and July 2000 were randomized to receive one of two luteal phase progesterone supplementation protocols. All patients underwent ovarian hyperstimulation using a luteal GnRH-agonist protocol, a ‘stop’ GnRH-agonist protocol, or a GnRH agonist microdose flare protocol, depending on individual patient characteristics. Patients began using 200 mg micronized progesterone vaginally TID beginning the morning of either day 3 following oocyte retrieval or beginning on day 6 following oocyte retrieval. All patients continued progesterone supplementation daily until a negative serum pregnancy test, or, if the patient became pregnant, until 10 weeks of gestation. Clinical pregnancy and implantation rates were compared. Results: All patients undergoing randomization received an embryo transfer. There were no differences in patient age, BMI, oocytes retrieved, or number of embryos transferred between the two groups. Those patients beginning progesterone support on day 6 following retrieval had a significantly lower pregnancy rate compared to those beginning on day 3 following retrieval (44.8% vs. 61.0%, p < 0.05). This difference in pregnancy rates was greater in those patients undergoing a luteal GnRH-agonist downregulation protocol (47.5% vs. 71.4%, day 6 vs. day 3, P = 0.03). Beginning progesterone on day 6 also significantly decreased implantation rates in the GnRH-agonist group (21.0% vs. 34.0%, day 6 vs. day 3, P = 0.02). Conclusions: Pregnancy rates are significantly decreased by initiating luteal phase supplementation later than day 3 following retrieval during IVF cycles. Despite elevated progesterone levels at the time of embryo transfer, progesterone supplementation should continue to be initiated at this time. Efforts to simplify medication regimens or to decrease treatment costs by decreasing the duration of progesterone supplementation should not be undertaken.

P-104. Open, multicentre, prospective, randomized study comparing r-hFSH therapy alone versus combination therapy (r-hFSH + r-hLH) in patients pituitary-desensitized with low dose luteal GnRH agonist protocol: preliminary results

P-104. Open, multicentre, prospective, randomized study comparing r-hFSH therapy alone versus combination therapy (r-hFSH + r-hLH) in patients pituitary-desensitized with low dose luteal GnRH agonist protocol: preliminary results

Improved controlled ovarian hyperstimulation in poor responder in vitro fertilization patients with a microdose follicle-stimulating hormone flare, growth hormone protocol

To assess the efficacy of a novel protocol-microdose GnRH agonist (GnRH-a), FSH, and GH, for the stimulation of IVF patients who were canceled previously on a standard luteal GnRH-a, FSH, GH protocol. Prospective evaluation using the patient's previous IVF stimulation attempt as historic controls. Private practice assisted reproductive technology center. Thirty-two patients who had prior ovulation induction cycles canceled using luteal phase GnRH-a suppression followed by exogenous gonadotropins and GH. Precycle treatment with oral contraceptives followed by follicular phase administration of 40 micrograms leuprolide acetate every 12 hours beginning on cycle day 3 and FSH supplemented with GH beginning on cycle day 5. Paired analysis of E2 day 5, number of follicles, ampules of FSH required, and cancellation rate. The number of oocytes, embryos, embryo quality, implantation rate, and pregnancy rate (PR) were determined for completed cycles on the microdose GnRH-a, FSH, GH protocol. Controlled ovarian hyperstimulation was superior during microdose GnRH-a, FSH, GH stimulation when compared with the prior luteal GnRH-a cycle. Specifically, there was a higher E2 response, more oocytes, fewer cycle cancellations, and no premature LH surge or luteinization. The microdose GnRH-a, FSH, GH protocol produced an average of 10 oocytes and a 50% ongoing PR. The microdose GnRH-a, FSH, GH protocol is superior to standard protocols for the treatment of patients with decreased ovarian reserve undergoing controlled ovarian hyperstimulation for IVF.

Premature luteinization during controlled ovarian hyperstimulation for in vitro fertilization-embryo transfer has no impact on pregnancy outcome

To determine if elevated serum P concentration on the day of hCG administration or P area under the curve (AUC) impacts on pregnancy rates (PRs) in IVF-ET cycles. Retrospective study. One hundred thirty-three couples underwent IVF-ET using luteal GnRH-agonist suppression followed by hyperstimulation with gonadotropins. Patient cycles were controlled for female age, ovarian reserve, male factor with intracytoplasmic sperm injection (ICSI), endometrial thickness and pattern, number of embryos, and number of high-quality embryos transferred, and cell stage at transfer. Pregnancy was defined as an ongoing pregnancy > 20 weeks. Patients and cycle parameters did not differ significantly based on the control parameters. Similar numbers of severe male factors treated by ICSI were in each group with similar PRs. Pregnancy rates and implantation rates did not differ based on P levels < or = 0.9, < or = 1.1, and < or = 1.4 ng/mL (conversion factor to SI unit, 3.18). Serum P concentrations per total eggs retrieved or per mature egg retrieved did not influence pregnancy outcome. Efficiency curves for serum P levels and P AUC did not demonstrate any differences in PR. At very high serum P (P > 2.0 ng/mL) samples size limits the ability of these data to rule out a negative effect. Serum P levels (and P AUC) commonly encountered during cycles of IVF-ET have no impact on pregnancy outcome.