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Female InfertilityAuthor's Note: The expert advisors for this article are James M. Goldfarb M.D., M.B.A., Director of Fertility Services, and Professor of Obstetrics & Gynecology at the Lerner College of Medicine, Cleveland Clinic Foundation, and Sandra P. Stewart, R.N., M.S., Clinical Nurse Specialist and Nurse Manager, both at the Cleveland Clinic Fertility Center in Beachwood, Ohio. Sandra Stewart is also my sister-in-law.
July 25, 2003 was the twenty-fifth birthday of Louise Brown, the first baby born after in vitro or assisted reproductive technology. Today, specialists in the field of Assisted Reproductive Technology (ART) marvel at the great good luck the doctors had in getting a successful outcome, given the technology, medications and plain old know-how that was not available in the 1970s. Currently, in Western countries, about 10-15% of couples experience some difficulty with fertility.(1) Remedies range from a visit to a primary physician, education and adjustments in timing attempts to conceive, to placing the entire reproductive process in the hands of a specialist. The Federal Centers for Disease Control (CDC) collects data (on treatment cycles) from fertility clinics on the special population of patients using assisted reproductive technology. Their latest figures, for women under 35, categorized causes as 40% female, 23% male, 17% combined male and female factors, 10% more than one female factor and 10% unexplained by any definable cause.(2)
What is Infertility, Subfertility, Sterility?
Different words are used to define different situations. Definitions have changed, as technology has changed.
Sterility is the absolute inability to procreate: an absent uterus in women, absent testes in men. In years past, a woman with blocked fallopian tubes or man with an obstructed vas deferens would be sterile. But with assisted reproductive technology (ART), this is no longer the case. Infertility is usually defined as no pregnancy after one year of unprotected intercourse. This is a relative measurement. Over time, many couples may achieve pregnancy. In five years, nearly one half of "infertile" couples will conceive.(1) Subfertility is used to describe gradations between normal fertility and sterility, often used interchangeably with infertility. Fecundability is the pregnancy rate from one menstrual cycle. The normal rate in humans is 20%. Seventy-five percent of normally fertile couples are expected to have conceived in six months and almost 100% by one year.(1) Normal fertility can be considered from several different points of view: the couple, the female and the male. In this article, we are going to look at female fertility: the biological steps and mechanisms, the defects, the causes of the defects and what to do. Three Basic Questions
There are really three basic questions that have to be answered when doctors try to determine why a woman is having problems getting pregnant.
A similar set of questions has to be answered in men. Is there sperm? Can it be delivered to the female? Is the sperm normal? In the male these questions are answered in a preliminary and rather thorough way by semen analysis. With women the process is more complicated. Before we look at causes and treatments, let's start with basic female function. Normal Female Fertility
Oogenesis
The female germ cells, called oogonia, lodge in the outer layer, or cortex, of the ovary. They divide rapidly and at the fifth month of a female fetus's life number up to 6-7 million cells. At that time, they begin maturation and are now called primary oocytes, eventually maturing to become primordial follicles. At birth, a female baby will have 2-4 million primordial follicles. In terms of numbers, birth is the high point, as many of the follicles will degenerate so that, by puberty, a woman will have, on average, about 400,000 of these follicles in her ovaries.(3) It has been generally accepted that these are all the germ cells a woman has for her lifetime because these cells have not been known to multiply during life the way the spermatogonia do. Although there is one recent article that suggests that germ cells in the ovary may be able to regenerate later in life,(4) in humans, for all practical purposes "what you have at birth is what you get for life" is still the case.
Follicle Development and Ovulation
Throughout female life from the onset of menstruation (menarche) to menopause, a small number of these primordial follicles are constantly beginning development. At puberty, hormones from the hypothalamus and pituitary glands in the brain will start to influence ovarian function. Without these hormones, the follices will not survive. The names of the hormones: gonadotropin releasing hormone (GnRH), follicle stimulating hormone (FSH) and luteinizing hormone (LH).(3)
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