The Impact of Serum Progesterone Levels on the Results of In Vitro Fertilization Treatments: A Literature Review.

The aim of this review is to analyze the relationship between preovulatory progesterone (P) rise and in vitro fertilization (IVF) pregnancy outcomes. It also investigates the sources and effects of rises in progesterone levels, including the underlying mechanisms and potential strategies in preventing its elevation during ovarian stimulation. Progesterone is produced in the early follicular phase in the adrenal gland, which shifts toward the ovaries prior to ovulation. Several factors contribute to the etiology of P level increase including the number of multiple follicles, the overdose of gonadotropins and poor ovarian response. Nowadays, the influence of the preovulatory P rise on IVF outcome remains controversial. Several authors have failed to demonstrate any negative impact, while others reported a detrimental effect associated with the rise of P. It seems that P rise (1.5 ng/ml or 4.77 nmol/l) may have deleterious effects on endometrial receptivity, namely, accelerating the endometrial maturation process that subsequently narrows the period for implantation and thus decreases pregnancy rates. Recent studies have proposed different cutoffs according to the ovarian response, which may be a little high in patients with high response in relation to those of normal response or low response. To prevent a P rise, it might be preferable to use milder stimulation protocols, earlier trigger of ovulation, cryopreservation of all embryos and transfer in the natural cycle.

Ovulation induction with a starting dose of 50 IU of recombinant follicle stimulating hormone in WHO group II anovulatory women: the IO-50 study, a prospective, observational, multicentre, open trial.

OBJECTIVE: To assess the efficacy and safety in clinical practice of a low dose regimen of 50 IU of recombinant follicle stimulating hormone in induction of ovulation. DESIGN: Prospective, observational, non-comparative, open, multicentre study. SETTING: Eighty-eight infertility clinics and teaching hospital fertility units throughout Spain. POPULATION: Women with normogonadotrophic chronic anovulation (WHO group II) with or without echographic diagnosis of polycystic ovary syndrome. METHODS: Low dose step-up protocol of recombinant follicle stimulating hormone administration (follitropin beta, Puregon) with a starting dose of 50 IU and weekly increments according to follicular response monitored prospectively by transvaginal ultrasonography. Patients were followed for a minimum of one cycle and a maximum of six. MAIN OUTCOME MEASURES: Rate and size of follicular growth, cumulative ovulation rate, follicle stimulating hormone doses and duration of treatment, pregnancy and cycle cancellation rate, ovarian hyperstimulation syndrome and multiple pregnancy. RESULTS: A total of 945 treatment cycles were evaluated. In 817 cycles, ovulation was induced with human chorionic gonadotrophin (hCG) and in 501 (61.3%) unifollicular development (a follicle of > or =18 mm) was achieved. A total of 128 cycles (13.5%) were cancelled because of ovarian hyper-responsiveness or spontaneous ovulation. The cumulative ovulation rate (confirmed by mid-luteal serum progesterone concentrations) after six treatment cycles was 84%. There were 136 clinical pregnancies (14.4% pregnancies per cycle). The cumulative pregnancy rate after six treatment cycles was 53.1%. Eight twin pregnancies occurred. Thirteen women miscarried and there were two cases of ectopic pregnancies. The median of average daily doses of follitropin beta in all cycles was 50 IU. Between 68% and 86% of patients received treatment with follitropin beta for a maximum of 14 days. Ovarian hyperstimulation syndrome occurred in 64 (6.8%) cases but no case of severe ovarian hyperstimulation developed. CONCLUSIONS: Low dose regimen of 50 IU of recombinant follicle stimulating hormone (Puregon) is efficient, safe and well tolerated for inducing follicular development in WHO group II anovulatory women.

Cost-effectiveness of recombinant versus urinary follicle-stimulating hormone in assisted reproduction techniques in the Spanish public health care system.

PURPOSE: To evaluate the relative cost-effectiveness of recombinant and urinary follicle-stimulating hormone (FSH) in assisted reproduction techniques in the Spanish National Health Service. METHODS: Markov modelling was used to compare costs and outcomes of three complete treatment cycles using recombinant or urinary FSH for controlled ovarian stimulation. Cost and effectiveness estimates were obtained from the literature and from Spanish clinicians. A Monte Carlo technique was used to randomise the distribution of outcomes at each stage. The analysis was performed by passing a virtual population of 100,000 patients through the computer simulation in each of 5000 Monte Carlo simulations. RESULTS: The cost per pregnancy was Euro12,791+/-1202 ($11,346+/-1066) with recombinant and Euro13,007+/-1319 ($11,537+/-1170) with urinary FSH (p < 0.0001). The mean number of cycles per pregnancy was 4.69 and 5.21, respectively. CONCLUSIONS: Recombinant FSH is more cost-effective than urinary FSH in the Spanish public health care system.