A Practical Approach, Second Edition=Ronald D. Ho.pdf

802 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITIONII. ADVERSE REPRODUCTIVE OUTCOMES TO STUDYA disturbance of reproductive function can result in a multitude of different adverse outcomes orendpoints for study. It is not necessary that a specific exposure causes all types of adverse outcomes.Some result in a very broad spectrum of disturbances, e.g., maternal alcoholism, which causesembryonic, fetal, and perinatal death, growth retardation, major and minor congenital malformations,and mental disturbances, including mental retardation. 2 Other agents may have a ratherspecific effect on only one or a few types of congenital malformations, e.g., the possible effect oflithium in increasing the risk for a congenital heart defect. 3 The full evaluation of the reproductivetoxicology of an agent therefore necessitates study of many different aspects of reproductiveoutcome. Even after such studies, it is always possible that the exposure results in a late, unexpectedeffect, as was the case with DES (diethylstilbestrol). 4A. Infertility and Subfertility1. Definition of Infertility and SubfertilityThe fertility of a couple will be a function of both male and female fertility. The fertility rate in apopulation will be affected by voluntary reduction of family size with the aid of contraceptivepractice and induced abortions.Female fertility depends on normal ovulation of a normal egg, its unimpaired passage through thefallopian tube to the uterus, thinning of the mucus surrounding the mouth of the cervix enabling thesperm to pass into the uterine cavity, and changes in the uterine lining enabling the fertilized egg toimplant. These processes are under endocrine regulation from the pituitary gland and the ovaries.Male fertility depends on the production of adequate numbers of healthy sperm in the testesand on the ability to achieve erection and ejaculation. Sperm production is under endocrine controlfrom the pituitary gland, and testicular hormone production is necessary for normal male genitalfunction.Infertility occurs when a couple is unable (without medical intervention) to have a child; thisis a rather frequent phenomenon. Ten percent or more of all couples trying to conceive will seekmedical help. In about half of the couples, male infertility is the cause and in about half, it is femaleinfertility.Modern medical technology often makes it possible to help these couples have children.Treatment will depend on the cause of the infertility. Examples are surgical opening of occludedfallopian tubes, fertility drug stimulation of the ovary and/or ovulation, and various types of invitro fertilization (IVF). Notably for male infertility, a special form of IVF called ICSI (intracytoplasmicsperm injection) can be used. The egg is then fertilized by one sperm cell, introduced intothe egg in vitro with micromanipulation.Subfertile couples have a reduced capability to achieve a pregnancy. They may have a pregnancyafter a longer delay than is usually the case. It is a matter of clinical judgement when a subfertilecouple is judged to be infertile—often 2 to 3 years of involuntary childlessness is needed beforeIVF procedures, for instance, are recommended.Exogenous causes may harm either the male or the female reproductive organs. Classicalexamples are male occupational exposure to dibromochloropropane, which resulted in a (temporary)arrest of spermatogenesis, 5 and prenatal female exposure to progestational agents or diethylstilbestrol,which has been said to affect future fertility. 62. Time to PregnancyA popular way to study an effect on fertility is to use the time taken to achieve pregnancy (TTP).This means the time (usually measured in months or menstrual cycles) it takes for a woman who© 2006 by Taylor & Francis Group, LLC