Infertility

For the purposes of this article, antiestrogens are compounds that counteract the biological activity of estrogens at the receptor level. In the late 1970s, there were no steroidal antiestrogens in widespread clinical use. Clomiphene [911 -45-5]( ) and tamoxifen/7(954(9-25 -/7(9) were nonsteroidal antiestrogens that had been employed for the treatment of female infertility and breast cancer, respectively. 

Reproductive System. The primary PGs are intimately involved in reproductive physiology (67). PGE2 and PGP2Q, are potent contractors of the pregnant utems and intravenous infusion of either of these compounds to pregnant humans produces a dose-dependent increase in frequency and force of uterine contraction. PGI2 and TXA2 have mild relaxant and stimulatory effects, respectively, on uterine tissue. The primary PGs also play a role in parturition, ovulation, luteolysis, and lactation and have been impHcated in male infertility. 

In 1956 selenium was identified (123) as an essential micronutrient iu nutrition. In conjunction with vitamin E, selenium is effective iu the prevention of muscular dystrophy iu animals. Sodium selenite is adrninistered to prevent exudative diathesis iu chicks, a condition iu which fluid leaks out of the tissues white muscle disease iu sheep and infertility iu ewes (see Eeed ADDITIVES). Selenium lessens the iacidence of pneumonia iu lambs and of premature, weak, and stillborn calves controls hepatosis dietetica iu pigs and decreases muscular inflammation iu horses. White muscle disease, widespread iu sheep and cattle of the selenium-deficient areas of New Zealand and the United States, is insignificant iu high selenium soil areas. The supplementation of animal feeds with selenium was approved by the U.S. EDA iu 1974 (see Eeed additives). Much of selenium s metaboHc activity results from its involvement iu the selenoproteia enzyme, glutathione peroxidase. 

The concept of hormonal control of ovulation first appeared in 1921 when Ludwig Habedandt, a physiologist at the University of Iimsbmck, showed that extracts of the corpus luteum, containing progesterone [57-83-0] C2 H2q02, could inhibit ovulation and make mice and rabbits infertile (10). Subsequent research showed that this phenomenon occurred in other species as well. 

Natural methods, ie, natural family planning, are methods based on awareness of the fertile and infertile segments of the menstmal cycle. This awareness can be utilized to avoid pregnancy or to become pregnant. 

In order to avoid conception, abstinence from sexual intercourse during the fertile period of the menstmal cycle must be practiced (77,104). It has been deterrnined that the fertile period in women occurs before menstmation (105,106), and formulas have been developed to determine the fertile and infertile days of the menstmal cycle. Ovulation has been linked to a cycHc shift in basal body temperature (107), which can be used retrospectively to determine the time of ovulation. 

PH-20, a guinea pig sperm protein of 64 kD, is present on both the plasma membrane and inner acrosomal membrane of sperm. It is essential for adhesion of sperm to the zona peUucida, the initial step in the fertilization process. Active immunization with PH-20 causes infertility in both male and female guinea pigs for a period ranging from 6 to 15 months (120). 

While considerable attention is given to the question of male fertility, the incidence of infertility or sub-fertility in the population is difficult to measure and it is not known to what extent measures of semen quality, for example, are indicators of male fertility as such. 

In more recent times, large doses of vitamin C have been claimed to prevent the common cold, cure infertility, delay the onset of symptoms in acquired immunodeficiency syndrome (AIDS), and inhibit the development of gastric and cervical cancers. None of these claims have been backed by medical evidence, however. In the largest study yet done of the effect of vitamin C on the common cojd, a meta-analysis of more than 100 separate trials covering 40,000 people found no difference in the incidence of colds between those who took supplemental vitamin G regularly and those who did not. When taken during a cold, however, vitamin C does appear to decrease the cold s duration by 8%. 

Aromatase inhibitors have also been used in premenopausal women for the treatment of endometriosis and to induce ovarian folliculogenesis as part of the treatment for infertility. 

The disruption of C1C-2 in mice leads to male infertility, blindness, and leukodystrophy, and was attributed to defective extracellular ion homeostasis in narrow clefts. C1C-2 yields currents that slowly activate upon hyperpolarization. It is also activated by cell swelling and by extracellular acidification. Structural determinants that are essential for these types of activation were identified by mutagenesis. There is a report that C1C-2 might be mutated in human epilepsy, but this has not been confirmed in fiuther studies. 

Hypogonadotropic hypogonadism is a genetically heterogeneous disorder characterized by infertility and... 

Analysis of ERa-deficient mice showed that both sexes are infertile and display a variety of phenotypic changes associated with the gonads, mammary glands, reproductive tracts, and skeletal tissues. In addition,... 

Mice models reveal that both PR foims are physiologically important. Mice lacking the PR gene fail to ovulate, are infertile, and have impaired thymic function. Selective PRA-deficient female mice are infertile due to reduced oocyte and uterine deficiency... 

Effect only seen in juvenile Effects reported from North Sea in the vicinity of shipping lanes Causes infertility and population decline in England, some without development of penis, but some recovery following 1987 ban on TBT use on small vessels... 

Tributyltin compounds used as antifouling agents on boats have had serious toxic effects upon many mollusks, including populations of oysters and dog whelks. Females of the latter species developed a condition known as imposex, which rendered them infertile and caused local extinction of the population in shallow coastal waters. Imposex provides the basis for a valuable biomarker assay. 

Setchell, K.D.R., Gossehn, S.J., and Welsh, M.B. et al. (1987). Dietary estrogens—a probable cause of infertility and liver-disease in captive cheetahs. Gastroenterology 93, 225-233. 

Cystic fibrosis (CF) is a recessive genetic disorder prevalent among whites in North America and certain parts of northern Europe. It is characterized by chronic bacterial infections of the airways and sinuses, fat maldigestion due to pancreatic exocrine insufficiency, infertility in males due to abnormal development of the vas deferens, and elevated levels of chloride in sweat (> 60 mmol/L). 

ADAMS N R, SANDERS M R (1988) Persisteut Infertility in Ewes After Prolonged Exposure to Oestradiol-17 Beta.. JReprod Fertil. 84 373-8. 

In some animals, consumption of a phytoestrogen-rich diet can cause temporary infertility and reproductive system disorders (Irvine, 1999). In humans, lower testosterone levels and a decline in human semen quality over the past century have been luiked to increased exposure to environmental endocrine disrupters (EDCs) (Sharpe and Skakkebaek, 1993). Furthermore, cases of sexual impotence have been reported in males exposed to synthetic estrogens in the pharmaceutical industry (Mattison et al., 1990). If this might be the case, the fetal-prepubertal period and Sertoli cell development would be of critical importance (Sharpe and Skakkebaek, 1993). However, an adverse effect of phytoestrogens on male fertility has yet to be proven. Recent work (Mitchell et al., 2001) addressing this point led to the conclusion that up to 40 mg/day of isoflavones over a two-month period had no effects on gonadotrophin and... 

Data on safety have been obtained from in vitro as well as in vivo animal and human studies (see also Section 10.4). About 50 years ago, Australian farmers observed an infertility syndrome in sheep associated with the consumption of clover species (Bennets et al., 1946). The clover compounds shown to cause the infertility (genistein, daidzein, equol, biochanin A, formononetin) were members of the isoflavone family (Bradbury and White, 1951 Shutt and Braden, 1968), raising the question of whether soy might cause infertility in humans (see also Section 10.4.9). A variety of reports further supported adverse effects of isoflavones on animal reproductive systems (Santell et al., 1997 Flynn et al., 2000a,b). 

---