In-vitro fertilization

Cosby NC, Dukelow WR. 1992. Toxicology of maternally ingested trichloroethylene (TCE) on embryonal and fetal development in mice and of TCE metabolites on in vitro fertilization. Fundam Appl Toxicol 19 268-274. 

Gonadotrophins are also used in assisted reproduction procedures. Here the aim is to administer therapeutic doses of FSH that exceed individual follicular FSH threshold requirements, thus stimulating multiple follicular growth. This, in turn, facilitates harvest of multiple eggs, which are then available for in vitro fertilization. This technique is often employed when a woman has a blocked fallopian tube or some other impediment to normal fertilization of the egg by a sperm cell. After treatment, the resultant eggs are collected, incubated in vitro with her partner s sperm, incubated in culture media until the embryonic blastocyst is formed, and then implanted into the mother s uterus. 

Pivotal pre-approval safety and efficacy was assessed in a randomized, open label, multicentre study of infertile females undergoing in vitro fertilization and embryo transfer. The primary efficacy parameter was the mean number of oocytes retrieved, which (at 13.6) was similar to the number retrieved when urinary-derived hCG was used. Serious potential side effects can include ovarian over/hyper-stimulation, sometimes with pulmonary or vascular complications. The product is marketed by Serono Inc. 

Embryonic stem cells are derived from pre-implant-stage human embryos, usually at the blastocyst stage (the blastocyst is a thin-walled hollow structure containing a cluster of cells, known as the inner cell mass, from which the embryo arises). These embryos are invariably ones initially generated as part of in vitro fertilization procedures but which are destined to be discarded, either due to poor quality or because they are in excess to requirement. There are an estimated 400 000 in vitro fertilization-produced embryos in frozen storage in the USA alone, of which some 2.8 per cent are likely to be discarded. 

Figure 14.17 Overview of the generation and culture of human embryonic stem cells. IVF in vitro fertilization. Refer to text for further details...

Holloway AJ, Moore HD, Foster PM. 1990. The use of in vitro fertility of female rats exposed to 1,3-dinitrobenzene. Fundam AppI Toxicol 14 113-122. 

Purified FSH is used to prepare follicles for in vitro fertilization because LH activity in menotropins may cause premature ovulation. Purified FSH is also used to treat infertility in women with polycystic ovarian disease in this disease LH and androgen production may already be elevated. 

Follicular fluid mutagenicity. In 24 patients, 12 smoking and 12 nonsmoking, who were treated in an in vitro fertilization program, the mutagenicity of follicular fluid was not influenced by the number of cigarettes smoked. However, urine samples of... 

Gonadotrophins are used in the treatment of amenorrhoea, infertility, cryptorchidism and hypogonadotrophic hypogonadism in males. It is also useful in in vitro fertilization. 

In infertile women choosing in vitro fertilization, naferelin in combination with gonadotrophins can be used for stimulating ovulation. It is also useful in management of uterine leiomyoma, benign prostatic hypertrophy, hirsutism and polycystic ovarian syndrome. 

Clomiphene is mainly used in the treatment of female infertility due to ovulatory failure and is also found useful to aid in vitro fertilization. 

G. Other applications Limited data show some beneficial effects of leuprolide in the treatment of breast cancer. According to Micromedex, there is good documentation that leuprolide is effective for bowel pain and nausea associated with irritable bowel syndrome. Leuprolide has been used for controlled ovarian hyperstimulation to enhance the in vitro fertilization-embryo transfer procedure. In endometriosis, the goal of treatment is pain relief and reduction of endometriotic lesions. In children with central precocious puberty, stimulated and basal gonadotropins are reduced to prepubertal levels. Testosterone and estradiol are reduced to prepubertal levels in males and females, respectively. 

G. Other applications Goserelin is useful for in vitro fertilization and is possibly effective in controlling precocious puberty and early puberty. Goserelin may promote fibroid regression, but rapid regrowth results upon discontinuation. 

Recommended dosage and monitoring requirements Once-daily subcutaneous doses of Antagon 250 pg have been effective for prevention of premature LH surges during ovarian stimulation in in vitro fertilization procedures. 

FSH, LH, and hCG are commercially available in several forms. They are used in states of infertility to stimulate spermatogenesis in men and to induce ovulation in women. Their most common clinical use is for the controlled ovulation hyperstimulation that is the cornerstone of assisted reproductive technologies such as in vitro fertilization (IVF, see below). 

Macklon NS et al The science behind 25 years of ovulation stimulation for in vitro fertilization. Endocr Rev 2006 27 170. [PMID 16434510]... 

An extensive variety of in vitro test systems are available that can be used in supplementary investigational studies of the reproductive system. Examples of these systems include the maintenance of whole organs (e.g., isolated perfused testis/ovary), primary culture of gonadal cells and subcellular fractions of organs and cells. In vitro fertilization techniques have also started to show promise in evaluating functional end-points for toxic effects. The information obtained from such test systems can be invaluable in identifying potential mechanisms of action... 

Many of the basic techniques for in vitro fertilization were established initially in the hamster (Yanagimachi et al., 1976), and the technique has been unreliable with other commonly used rodent species. A number of studies have shown that this technique can be... 

Heterologous in vitro fertilization or, perhaps more correctly, sperm-oocyte penetration studies have also received attention. The most extensively used bioassay of this type has been the zona-free hamster oocyte test (WHO, 1999), which investigates the ability of human sperm to penetrate and fuse with the oolemma of a hamster oocyte denuded of its zona pellucida. 

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