http://link.springer.com/content/pdf/10.1007/978-3-642-60390-7_28.pdf

The Endocrinology of Pregnancy

Background
Progesterone, a female sex hormone, is known to induce secretory changes in the lining of the uterus essential for successful implantation of a fertilized egg. It has been suggested that a causative factor in many cases of miscarriage may be inadequate secretion of progesterone. Therefore, progestogens have been used, beginning in the first trimester of pregnancy, in an attempt to prevent spontaneous miscarriage.

Objectives
To determine the efficacy and safety of progestogens as a preventative therapy against miscarriage.

Search methods
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 August 2013), reference lists from relevant articles, attempting to contact authors where necessary, and contacted experts in the field for unpublished works.

Selection criteria
Randomized or quasi-randomized controlled trials comparing progestogens with placebo or no treatment given in an effort to prevent miscarriage.

Data collection and analysis
Two review authors assessed trial quality and extracted data.

Main results
Fourteen trials (2158 women) are included. The meta-analysis of all women, regardless of gravidity and number of previous miscarriages, showed no statistically significant difference in the risk of miscarriage between progestogen and placebo or no treatment groups (Peto odds ratio (Peto OR) 0.99; 95% confidence interval (CI) 0.78 to 1.24) and no statistically significant difference in the incidence of adverse effect in either mother or baby.

A subgroup analysis of placebo controlled trials did not find a difference in the rate of miscarriage with the use of progestogen (10 trials, 1028 women; Peto OR 1.15; 95% CI 0.88 to 1.50).

In a subgroup analysis of four trials involving women who had recurrent miscarriages (three or more consecutive miscarriages; four trials, 225 women), progestogen treatment showed a statistically significant decrease in miscarriage rate compared to placebo or no treatment (Peto OR 0.39; 95% CI 0.21 to 0.72). However, these four trials were of poorer methodological quality. No statistically significant differences were found between the route of administration of progestogen (oral, intramuscular, vaginal) versus placebo or no treatment. No significant differences in the rates of preterm birth, neonatal death, or fetal genital anomalies/virilization were found between progestogen therapy versus placebo/control.

Authors' conclusions
There is no evidence to support the routine use of progestogen to prevent miscarriage in early to mid-pregnancy. However, there seems to be evidence of benefit in women with a history of recurrent miscarriage. Treatment for these women may be warranted given the reduced rates of miscarriage in the treatment group and the finding of no statistically significant difference between treatment and control groups in rates of adverse effects suffered by either mother or baby in the available evidence. Larger trials are currently underway to inform treatment for this group of women.

Progestogen for preventing miscarriage

https://www.scielo.br/pdf/clin/v68s1/a03v68s1.pdf

The epidemiology and etiology of azoospermia

Background
Miscarriage is a common complication encountered during pregnancy. The role of progesterone in preparing the uterus for the implantation of the embryo and its role in maintaining the pregnancy have been known for a long time. Inadequate secretion of progesterone in early pregnancy has been linked to the aetiology of miscarriage and progesterone supplementation has been used as a treatment for threatened miscarriage to prevent spontaneous pregnancy loss.

Objectives
To determine the efficacy and the safety of progestogens in the treatment of threatened miscarriage.

Search strategy
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (December 2009) and bibliographies of all located articles for any unidentified articles.

Selection criteria
Randomized or quasi-randomized controlled trials that compare progestogen with placebo, no treatment or any other treatment given in an effort to treat threatened miscarriage.

Data collection and analysis
At least two authors assessed the trials for inclusion in the review and extracted the data.

Main results
Two studies (84 participants) were included in the meta-analysis. In one study, all the participants met the inclusion criteria and in the other study, only the subgroup of participants who met the inclusion criteria was included in the meta-analysis. There was no evidence of effectiveness with the use vaginal progesterone compared to placebo in reducing the risk of miscarriage (risk ratio 0.47; 95% confidence interval 0.17 to 1.30).

Authors' conclusions
Based on scarce data from two methodologically poor trials, there is no evidence to support the routine use of progestogens for the treatment of threatened miscarriage. Information about potential harms to the mother or child, or both, with the use of progestogens is lacking. Further, larger, randomized controlled trials on the effect of progestogens on the treatment of threatened miscarriage, which investigate potential harms as well as benefits, are needed.

/pdf/progestogen-for-treating-threatened-miscarriage-22xdjpmk9u.pdf

Progestogen for treating threatened miscarriage.

Efficacy of progesterone support for pregnancy in women with recurrent miscarriage. A meta-analysis of controlled trials.

Between 1983 and 1984 a double-blind randomized study with progesterone substitution in threatened abortion was carried out. Fifty-six patients with vaginal bleeding during the first trimester of pregnancy, the internal cervical os being closed, were referred to the hospital. Twenty-five women (5th and 6th week of gestation) with positive serum concentrations of beta-hCG were admitted to the study without regard to sonogram results. In other 25 women (7th-10th week of pregnancy) and 6 women (greater than or equal to 11th week of pregnancy) fetal heart action and movement could be demonstrated by ultrasound. The patients were prescribed bed rest and vaginal suppositories twice daily, containing either 25 mg progesterone or only polyethylene glycol. The code was not broken until after completion of the study. Serial serum determinations of beta-hCG, estradiol-17 beta (E2), progesterone, and ultrasound were performed. Four patients had to be omitted from final analysis (two tubal pregnancies, one intrauterine infection, one sectio parva). Three of 26 patients progesterone (11%) and five of 26 patients with placebo (19%) had an abortion, which represented no significant difference. Frequency of abortion was increased in women more than 30 years old, in women with previous abortions and after ovulation induction. Progesterone treatment resulted in a significant elevation of serum progesterone concentrations (p less than 0.01), while beta-hCG and E2 were unchanged. The results of this study confirm that pregnancy outcome is favorable in women with bleeding and normal hormone concentrations without hormonal treatment and unfavorable in women with reduced beta-hCG and E2-concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-blind controlled trial of progesterone substitution in threatened abortion.

The role of serum prolactin (sPRL) in male infertility is still unclear. For assessing the clinical significance of prolactin determination during infertility investigation, serum samples of 204 males attending the Infertility Clinic of Heidelberg were examined during a 1-year period. None of the patients exhibited galactorrhoea or complained of impotence. Results were correlated with age, duration of infertility, sperm count, motility, morphology, viability, and other parameters of routine sperm analysis and postcoital testing (PCT). Additionally, in vitro sperm penetration testing (SCMPT) in cervical mucus of partners and donors was performed as an important measure of functional sperm capacity. The subsequent pregnancy rate was determined after 6 months. Prolactin levels ranged from 1.4 to 24.7 ng/mL, with a median of 5 ng/mL. Only one patient had prolactin levels out of the normal range (greater than 20 ng/mL). No significant correlation of sPRL concentration was found with results of semen analysis, PCT outcome, or SCMPT. The functional sperm capacity was better in the groups of patients with sPRL above the median level (P less than .005). No significant difference in pregnancy rate was found between the high (greater than 5 ng/mL) and low (less than or equal to 5 ng/mL) prolactin groups; these were 20% and 26%, respectively. The results suggest that routine screening of asymptomatic male patients during infertility investigation for sPRL concentration is not helpful for assessing fertility prognosis. Prolactin should be preferentially determined in patients with clinical symptoms of hyperprolactinemia to exclude pituitary adenoma.

Influence of serum prolactin on semen characteristics and sperm function.

Semen samples from 179 patients with longstanding infertility were allowed to penetrate capillaries filled with a fraction of fresh hens' egg white (HEW) as a substitute for cervical mucus (CM) for the in-vitro sperm-cervical mucus penetration test (SCPMT). Results were correlated with those obtained from human CM (HCM) used in parallel on the same semen sample, compared to results of sperm analysis and post-coital testing (PCT) and analysed for their prognostic value for a subsequent pregnancy in a prospective study. The overall pregnancy rate after 6 months was 26.3% (47/179). Whereas routine semen analysis (semen volume, pH, sperm count, progressive motility, morphology and fructose concentration) did not differentiate between patients who achieved pregnancy and those who did not, significant differences were found for the penetration distance (P less than 0.02) and the motility grade of sperm in HEW (P less than 0.02). Although the mean sperm velocity in HEW was reduced compared to HCM, a close positive correlation was found between the sperm density and the penetration distance (P less than 0.001). The percentage of samples with good HEW penetration increased significantly in parallel with better results of post-coital testing (P less than 0.001). The results indicate that, when fresh human CM is not available, HEW can be used as a medium for the SCPMT as a valuable adjunct to semen analysis which provides information about sperm functional capacity.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2605.1990.tb01030.x

B. Runnebaum

Papers

Double-blind controlled trial of progesterone substitution in threatened abortion.

Influence of serum prolactin on semen characteristics and sperm function.

The use of hens' egg white as a substitute for human cervical mucus in assessing human infertility.