Maria Luisa Casini

Effects of the position of fibroids on fertility

This prospective, controlled study was performed in order to evaluate whether the location of uterine fibroids may influence reproductive function in women and whether removal of the fibroid prior to conception may improve pregnancy rate and pregnancy maintenance. We examined 181 women affected by uterine fibroids who had been trying to conceive for at least 1 year without success. The main outcome measures were the pregnancy rate and the miscarriage rate. Among the patients who underwent myomectomy, the pregnancy rates obtained were 43.3% in cases of submucosal, 56.5% in cases of intramural, 40.0% in cases of submucosal–intramural and 35.5% in cases of intramural–subserosal uterine fibroids, respectively. Among the patients who did not undergo surgical treatment, the pregnancy rates obtained were 27.2% in women with submucosal, 41.0% in women with intramural, 15.0% in women with submucosal–intramural and 21.43% in women with intramural–subserosal uterine fibroids, respectively. Although the results were not statistically significant in the group of women with intramural and intramural–subserosal fibroids, this study confirms the important role of the position of the uterine fibroid in infertility as well as the importance of fibroids removal before the achievement of a pregnancy, to improve both the chances of fertilization and pregnancy maintenance.

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.

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.

Inhibition of heat-induced denaturation of albumin by nonsteroidal antiinflammatory drugs (NSAIDs): Pharmacological implications

The activity of nonsteroidal antiinflammatory drugs (NSAIDs) in rheumatoid arthritis is not only due to the inhibition of the production of prostaglandins, which can even have beneficial immunosuppressive effects in chronic inflammatory processes. Since we speculated that these drugs could also act by protecting endogenous proteins against denaturation, we evaluated their effect on heat-induced denaturation human serum albumin (HSA) in comparison with several fatty acids which are known to be potent stabilizers of this protein. By the Mizushimas assay and a recently developed HPLC assay, we observed that NSAIDs were slightly less active [EC50∼10−5-10−4 M] than FA and that the HPLC method was less sensitive but more selective than the turbidimetric assay, i.e. it was capable of distinguishing true antiaggregant agents like FA and NSAIDs from substances capable of inhibiting the precipitation of denatured protein aggregates. In conclusion, this survey could be useful for the development of more effective agents in protein condensation diseases like rheumatic disorders, cataract and Alzheimers disease.

An infertile couple suffering from oligospermia by partial sperm maturation arrest: can phytoestrogens play a therapeutic role? A case report study.

We describe the case of a 30-year-old man with severe oligospermia, caused by partial sperm maturation arrest at spermatidic stage, who was given phytoestrogens. The couple had been trying to conceive for 3 years. The woman was normal at the clinical and endocrinological examination. No other parameters except sperm count, motility and morphology were altered in the male subject. Semen analysis was performed at baseline and after 3 and 6 months of therapy, which consisted of phytoestrogens 80 mg/day for 6 months. An additional semen analysis was performed 6 months after the termination of therapy (wash-out period). During the third month semen parameters improved drastically; therefore a reproductive technique (intrauterine insemination) was performed. This treatment resulted in pregnancy, and a healthy baby weighing 3300 g was born. After 6 months of treatment, sperm parameters ameliorated further. Conversely, after the wash-out period, they returned to baseline values. The appealing results strongly suggest a therapeutic role for phytoestrogens in the treatment of oligospermia. However, it is evident that a validation stage and randomized, controlled studies are essential in order to confirm this observation and verify that phytoestrogens can play an important role in male infertility.

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.

Development of a Turbidimetric Assay to Study the Effect of Urinary Components on Calcium Oxalate Precipitation

The pharmacological treatment of calcium urinary stones, most of which are made of calcium oxalate (CaOx), is only prophylactic. The causes of nephrolithiasis are often unclear, and a number of patients were found to be deficient in physiological inhibitors, e.g. citrate, pyrophosphate, magnesium, and specific proteins. The identification and characterization of these inhibitors can be performed in vitro by a number of methods, most of which are complex and time-consuming. Thus, we developed a simple turbidimetric method based on the precipitation of CaOx from a supersaturated solution. Using this approach, we determined that ionic strengths >0.2 and pH <5 inhibited the precipitation of CaOx. The first observation is of interest if one considers that the osmolarity of urine varies in the range of 50–1,400 mmol/kg, while the effect of pH is not usually seen in vivo because of the influence of other phenomena, such as the precipitation of uric acid. The activity of sodium chloride, magnesium and citrate was displayed at concentrations not far from their normal urinary level. Among several mono-, di- and tricarboxylic acids, like acetic, ascorbic, citric, isocitric, formic, fumaric, gluconic, glutaric, α-ketoglutaric, maleic, malic, malonic, propionic, pyruvic, succinic, and tartaric acid, only isocitric acid was more potent than citric acid. Pyrophosphate was a potent inhibitor in vitro, but its urinary level may not be sufficient for a significant effect in vivo. Amino acids like Ala, Arg, Asp, Glu, Gly, and Ser, which are known to bind calcium, showed little activity. Work is in progress to search for new compounds potentially useful in the treatment of nephrolithiasis.

Development of an HPLC Assay to Study the Effect of Endogenous and Exogenous Substances on Heat-Induced Aggregation of Human Serum Albumin

Abstract The mechanism of action of non-steroidal anti-inflammatory drugs which are used in high doses in chronic inflammatory conditions is not clearly understood. Their known protein-stabilizing properties could play a significant role. The inhibition of cyclooxygenase may not be essential for their anti-rheumatic activity, since compounds with strong anti-denaturant properties and devoid of anti-inflammatory activity were shown to be effective in an experimental model of rheumatoid arthritis. Hence, to develop new anti-rheumatic drugs it is essential that a simple in vitro method to evaluate the anti-denaturant activity of endogenous and exogenous compounds is available. We developed a new assay, using gel permeation high performance liquid chromatography, to study the effect of endogenous and exogenous compounds on heat-induced aggregation of human serum albumin in conditions in which protein precipitation does not occur. Non-steroidal anti-inflammatory drugs like diclofenac, ibuprofen and naproxen inhibited the aggregation of albumin at low concentrations (EC50 10−4–10−5 mol/l) comparable to those active in a classical turbidimetric method, whereas the effect of weak stabilizers, like sodium cloride and formic, fumaric, maleic, malonic, and succinic acid (EC50 10−1–10−2 mol/l in the Mizushima test) was not detectable. Furthermore, the HPLC assay allowed the examination of a number of coloured substances, including bilirubin, which appeared to be a strong stabilizer of its physiological carrier, albumin. These data could be clinically relevant, since the drugs examined are used at very high doses in rheumatoid arthritis and related conditions, with plasma levels that could cause significant stabilization of serum albumin and perhaps other proteins.

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.