Pharmacodynamics of combined estrogen–progestin oral contraceptives: 4. Effects on uterine and cervical epithelia

ABSTRACT

Introduction: Steroid hormones are responsible for specific changes in the endometrium during the menstrual cycle, when they are sequentially secreted and, because of this, in the early days sequential combined oral contraceptive regimens were utilized. The same basic concept has been utilized with multi-phasic regimens, in order to produce endometrial pictures mimicking the normal cycle.

Areas covered: The Endometrial effects of progestins and estrogens; combined monophasic high- (50 μg), medium- (30 μg), low- (20 μg), ultralow- (15 μg) estrogen content; sequential regimens; multiphasic combinations; treatment schedules.

Cervical effects of combined high-dose and sequential combinations, including evidence for an increase in malignant lesions.

Expert opinion: Overall, combined oral contraceptives (COCs) inhibit normal proliferative changes and the endometrium becomes thin, narrow, with widely spaced glands and pre-decidual changes in the stroma. During the first few cycles the progestin induces a coexistence of proliferative and secretory features; with time, the picture changes because the progestin induces a down-regulation of estrogen receptors, resulting in tortuous glands similar to those in the secretory phase, but characterized by a quiescent, atrophic glandular epithelium.

In the cervical epithelium, under the influence of high-dose COCs, endocervical glands became hypersecretory and in some instances, distinctive type of atypical polypoid endocervical hyperplasia is found.     

Ovum recovery after microsurgical reanastomosis of the rabbit oviduct

Causes for failure of pregnancy after tubal reconstructive surgery are incompletely understood. The impact of microsurgical resection reanastomosis on ovum recovery was studied in the rabbit oviduct. One hundred sixty rabbits were divided into three groups: one experimental group in which a resection reanastomosis was made in the ampullar or isthmic tubal segment, respectively, and two control groups. After mating, ovum recovery was evaluated. In ampullary operated oviducts the ovum recovery rate was significantly lower compared with recovery rates in isthmically operated and in control oviducts. Furthermore, in ampullary operated oviducts peritoneal transmigration of ova was frequently observed. Disturbances in ovum pickup from the ovarian surface or the peritoneal cavity seem to be responsible for the decrease in recovery rate found in the ampullary operated oviducts.     

Investigation of the infertile couple: when is the appropriate time to explore female infertility?

While the appropriate method for the investigation of female infertility continues to be debated, the timing of the investigation has received less attention. The current approach is time-consuming, and paradoxically may lead to overtreatment as well as undertreatment. Recent findings on fecundity and the conception window in humans have important implications for the timing of the investigation of female infertility. The findings support the view that fertility-oriented intercourse may have a major impact in reducing the time to pregnancy. Procedures for the investigation of female infertility are becoming less invasive and more accurate, while the therapies for infertility are more effective. It is proposed that under appropriate circumstances female infertility should be investigated after 6 months of fertility-oriented intercourse.     

Evaluation of recombinant tissue-type plasminogen activator in adhesion prevention and neoangiogenesis in a rat experimental adhesion model

This study was designed to test the effect of recombinant tissue-type plasminogen activator (rt-PA) in reducing adhesion formation and to observe its influence on peritoneal neoangiogenesis. In 20 Wistar rats, a 4-cm midline incision was made, and a square piece of Silastic, 0.5×0.5 cm and 0.2 mm thick, was fixed on the right side of the peritoneum with two separate angular stitches of nylon 9/O. The rats were randomized into two groups of 10 animals each. In the first group we injected 0.2 mg of rt-PA intraperitoneally three times a day. The second group of 10 rats was used as a control group. Each rat was reoperated on day 12. Intraperitoneal injection of rt-PA seemed not to affect adhesion formation, as a 100% adhesion rate was reported in the treated group compared with 90% of the control group. The results showed that rt-PA acts on the neoangiogenesis involved in postsurgical adhesion formation by reducing the size and length of the vessels. This action seems to slow down peritoneal healing with a negative effect on postsurgical adhesion prevention.     

Promoting awareness of neonatal menstruation

Neonatal uterine bleeding (NUB) has been carefully studied in the past through case reports, small series, clinical cohort studies, pathology investigations of fetal and neonatal. Following a historical recount, this review summarizes biological mechanisms conditioning NUB, starting from the persistence till birth of an 'ontogenetic progesterone resistance' (OPR), causing decreased responsiveness of target tissues to bioavailable progesterone. Several pregnancy-related conditions, such as preeclampsia, fetal growth restriction, prematurity, post-maturity and even Rhesus or ABO incompatibility, influence the occurrence of NUB. It seems therefore that the phenomenon is precipitated by chronic fetal distress. When present, OPR may persists until telarche; as a consequence, if pregnancy occurs in early teenage, the disorder known as “defective deep placentation” may ensue, increasing the risk of obstetrical syndromes. In the presence of NUB, retrograde shedding into the peritoneal cavity of endometrial stem/progenitor and niche cells may occur. There, given the right environment, these cells can survive and become activated at the time of telarche, causing the specific phenotype of early-onset endometriosis. In conclusion, neonatal menstruation is a fetal distress indicator and can alter the incidence of a variety of pathological conditions later in life. For this reason, it should be carefully recorded and the parents informed.