Loredana Costabile

High dose of phytoestrogens can reverse the antiestrogenic effects of clomiphene citrate on the endometrium in patients undergoing intrauterine insemination: a randomized trial.

Objective: To compare the effectiveness of clomiphene citrate (CC) alone or combined with phytoestrogens (PE) in ovulation induction in patients who had intrauterine insemination in a randomized, double-blind study. Methods: A total of 134 women aged 25-35 years, who were infertile for at least 2 years and who had oligomenorrhea or amenorrhea associated with a positive menstrual response to the intramuscular progesterone-challenge test were enrolled. They were randomly treated with CC (100 mg daily for 5 days) and CC (100 mg daily for 5 days) in combination with PE (1500 mg daily for 10 days). We estimated the difference in uterine artery pulsatily index, number of preovulatory follicles, endometrial thickness, and pregnancy rate. Results: Both treatments increased follicle-stimulating hormone, luteinizing hormone, and 17β-estradiol plasma concentrations, but the differences were not statistically significant. However, the differences in endometrial thickness of the two groups were statistically significant. No significant differences in the pulsatility index values and in the number of preovulatory follicles were noted. Conclusion: A high dose of phytoestrogens can reverse the deleterious effects of clomiphene citrate on endometrial thickness and could contribute to higher pregnancy rates.

A prospective randomized study comparing intramuscular progesterone and 17α-hydroxyprogesterone caproate in patients undergoing in vitro fertilization–embryo transfer cycles

Abstract Objective: To compare the effectiveness of i.m. P and 17α-hydroxyprogesterone caproate (17-HPC) for luteal phase support, in patients undergoing IVF-ET cycles. Design: Prospective, randomized study. Setting: Patients undergoing IVF-ET in our Centers. Patient(s): The inclusion criteria were the use of GnRH down-regulation and aged Intervention(s): A total of 300 cycles were randomly treated with either 17-HPC (341 mg every 3 days) or P (50 mg daily). Main Outcome Measure(s): The outcomes of IVF in both study groups were evaluated for biochemical pregnancy, miscarriage, clinical pregnancy, and ongoing pregnancy. Result(s): No difference was found in the main outcome parameters considered. Conclusion(s): Although the results of the study encourage the use of 17-HPC for luteal phase support in patients undergoing IVF-ET program, more studies are necessary to support the hypothesis that it can replace i.m. P-in-oil.

Low Dose of Ethinyl Estradiol Can Reverse the Antiestrogenic Effects of Clomiphene Citrate on Endometrium

Fifty healthy, voluntary patients aged between 20 and 30 years with regular menstruation and plasmatic progesterone level >10 ng/ml at the midluteal phase have been enrolled in this study. They were randomly treated with clomiphene citrate (CC; group A) or CC + ethinyl estradiol (0.05 mg group B, or 0.02 mg group C). We estimated the difference in uterine artery pulsatily index, endometrial thickness and histological dating and morphometric analysis of endometrium. No significant differences in Pulsatility Index values and in the number of preovulatory follicles were noted. The difference between endometrial thickness, histological dating and morphometric analysis of the endometrium were statistically different between groups B and C vs. A. Our study shows that CC has a deleterious effect on endometrium maturity and that adding ethinyl-E2 produces a favorable endometrial response even with very low doses.

Ovulation induction with urinary FSH or recombinant FSH in polycystic ovary syndrome patients: a prospective randomized analysis of cost-effectiveness.

The aim of this prospective, randomized trial was to compare the clinical results and the cost-effectiveness of urinary FSH (uFSH) and recombinant FSH (rFSH) in ovarian stimulation for intrauterine insemination (IUI) cycles in polycystic ovary syndrome (PCOS) patients. One-hundred and seventy PCOS infertile patients undergoing IUI were enrolled, and protocols of ovarian stimulation with uFSH or rFSH were randomly assigned. The total number of cycles performed was 379 (182 and 197, respectively). The main outcome measures were the number of mature follicles, the days of stimulation, the number of ampoules and IU used per cycle, the biochemical/clinical pregnancy rates, the number of multiple pregnancies and the cost-effectiveness. No statistically significant differences were found in the follicular development, length of stimulation, pregnancy rates, delivery rates and multiple pregnancies between the two groups. In the uFSH group, the cost per cycle remained significantly lower (218.51 +/- 88.69 versus 312.22 +/- 118.12; P < 0.0001), even though a significantly higher number of IU of gonadotrophins were used (809.3 +/- 271.9 versus 589.1 +/- 244.7; P < 0.0001). The cost-effectiveness (i. e. within a group, the total cost of all cycles divided by no. of clinical pregnancies) was 1729.08 in the uFSH group and 3075.37 in the rFSH group. In conclusion, uFSH and rFSH demonstrated the same effectiveness in ovarian stimulation in IUI cycles in PCOS patients. The urinary preparation is more cost-effective due to the difference of its cost per IU.

Use of Intramuscular Progesterone versus Intravenous Albumin for the Prevention of Ovarian Hyperstimulation Syndrome

This study was designed to compare the effectiveness of intramuscular progesterone with that of intravenous albumin in the prevention of ovarian hyperstimulation syndrome (OHSS). Ninety-six patients at high risk to develop OHSS (estradiol concentration >9,000 pmol/l on the day of hCG administration and over 20 follicles of a diameter larger than 14 mm observed by transvaginal ultrasonography) and undergoing in vitro fertilization-embryo transfer were enrolled. They were randomly treated with intramuscular progesterone (200 mg/day) or 100 ml of 20% intravenous albumin in order to estimate the difference in the incidence of OHSS. A significant difference in the incidence of moderate OHSS and no cases of severe OHSS were observed between the groups. Our data show the effectiveness in preventing OHSS with high doses of progesterone.

Diclofenac pyrrolidine versus Ketoprofen for the relief of pain from episiotomy: A randomized controlled trial

Background.  The treatment of pain from episiotomy or from tearing of perineal tissues during childbirth is often unapplied, although discomfort may be severe. We performed a randomized double‐blind controlled trial to compare the effectiveness and side‐effects of two analgesics in the management of postpartum perineal pain. Patient preference toward the two medications was also analyzed.

17α-Hydroxyprogesterone caproate versus intravaginal progesterone in IVF-embryo transfer cycles: a prospective randomized study

One of the main issues in the management of IVF and embryo transfer techniques is to ensure adequate concentrations of progesterone. The aim of this prospective, randomized study was to compare the effectiveness of 17α-hydroxyprogesterone caproate (17-HPC) administered intramuscularly and intra-vaginal progesterone in gel in luteal phase support in patients undergoing IVF–embryo transfer cycles. A total of 320 patients were randomly treated with either 17-HPC (341 mg i.m. every 3 days) or progesterone vaginal gel (90 mg daily). The inclusion criteria were the use of gonadotrophin-releasing hormone down-regulation and age <40 years. The outcome of IVF in both study groups was evaluated for implantation rate, biochemical pregnancy, clinical pregnancy, miscarriage, and ongoing pregnancy rate. The results of this study showed that 17-HPC conferred more benefit to IVF–embryo transfer cycles compared with intra-vaginal progesterone, as demonstrated by the results of most of the main outcome parameters considered. The data showed that 17-HPC administered every 3 days appears to be more effective in providing luteal support in comparison to intra-vaginal progesterone.

Different routes of progesterone administration and polycystic ovary syndrome: a review of the literature.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in woman of reproductive age. Although extensive studies have been performed in past decades to investigate the pathobiological mechanisms underlying the unset of this disease, its etiology remains unknown. Progesterone is a hormone of paramount importance in ovulation, implantation and luteal phase support. Low levels of progesterone have been found in the early luteal phase in PCOS patients. Granulosa cells from polycystic ovaries show an altered progesterone production. Moreover, the lack of cyclical exposure to progesterone may have a role in the development of the gonadotropin and androgen abnormalities found in PCOS patients. Ovulation failure and progesterone deficiency may facilitate the hypothalamic–pituitary abnormalities causing the associated disordered luteinizing hormone secretion in PCOS. Progesterone may be administered to PCOS patients in the following cases: to induce withdrawal bleeding, to suppress secretion of luteinizing hormone, in ovulation induction in clomiphene citrate-resistant patients and in luteal phase support in assisted reproduction. We discuss the pharmacologic characteristics of the different routes of progesterone administration with reference to these diverse indications, the therapeutic objectives and patient compliance.

Efficacy and safety of 17α-hydroxyprogesterone caproate in hormone replacement therapy

The aim of the present study was to evaluate the efficacy (in terms of induction of uterine bleeding) and safety (in terms of absence of endometrial hyperplasia) of 17α-hydroxyprogesterone caproate (17α-HPC) in a therapeutic regimen for hormonal replacement after menopause. Fifty postmenopausal patients received hormone replacement therapy (HRT) for 24 weeks. The treatment regimen consisted of standard estrogen replacement therapy at commonly prescribed doses for the prevention of climacteric symptoms and 341 mg of 17α-HPC every 30 days. Enrolled women were told to expect withdrawal bleeding 7–10 days after the administration of 17α-HPC. Forty-eight patients completed the trial. In 91.7% of cases, patients experienced the expected pattern, i.e., strict withdrawal bleeding exclusive of any other form of bleeding. Breakthrough bleeding and/or other forms of abnormal bleeding affected only four women. At the 6th month none of the endometrial samplings motivated by endometrial thickness >10 mm and evidence of heterogeneous echogenicity (two cases) was positive for carcinoma. No biopsies had to be performed at the end of the 12th month of treatment. No serious adverse effect where recorded during the study period. In conclusion, our data show the efficacy and safety of 17α-HPC in HRT.