Advances in the Treatment of Ovulatory Dysfunction

Etiologies And Diagnostic Approach To Ovulatory Dysfunction
(PART ONE OF TWO)
(April 2005)

Mark P. Trolice, M.D., FACOG, FACS
Board Certified, Reproductive Endocrinology And Infertility
Director, Fertility C.A.R.E.

• Overview Of Ovulatory Dysfunction
• Causes and Diagnosis
• Read Part Two

Overview Of Ovulatory Dysfunction

Ovulatory dysfunction represents one of the most common causes of female infertility. In part 1 of this 2 part series we will review the etiologies and diagnostic approach to ovulatory dysfunction.

Part 2 will outline current treatment options as well as several recent pharmacologic advances.

Normal ovulation requires precise synergism between the ovary and the neuro-endocrine system. Subtle abnormalities in either of these systems can often result in significant ovulatory disturbances.

During normal ovulation GnRH is released in a pulsatile fashion and reaches the anterior pituitary via the portal circulation. This in turn results in pituitary release of the peptide hormones follicle stimulating hormone (FSH) and luteinizing hormone (LH).

Together, these gonadotrophic hormones stimulate follicular growth usually culminating in the production of a dominant follicle and ovulation. The resulting oocyte can then be fertilized if spermatozoa are present in the fallopian tubes during the first 24 hours after ovulation.

Without regular ovulation the likelihood of pregnancy is significantly reduced. However, in women with normal ovulatory function the likelihood of conception is approximately 20% per month. Any abnormality that disrupts the normal ovulatory process can result in reduced ability to conceive (sub fertility) or infertility, defined as 12 months of unprotected intercourse without pregnancy.

Although the clinical presentation may be variable, most women who do not ovulate also do not menstruate. Ovulatory dysfunction is likely to be present in women with irregular, infrequent menstrual cycles (oligomenorrhea) or too frequent cycles (polymenorrhea). In women complaining of amenorrhea disordered ovulation is almost always present.

Conversely, regular menstrual cycles, with cycle length between 22 and 35 days, and the presence of recurring premenstrual symptoms suggest the presence of ovulatory cycles. However, while regular monthly bleeding is highly suggestive of ovulation, a resulting pregnancy provides the only definitive proof of ovulation. Significantly, approximately 20 percent of PCOS patients have monthly cycles but do not ovulate.

Causes and Diagnosis

In reproductive age patients presenting with menstrual or ovulatory abnormalities several important disorders should be considered. While some causes are readily identified others may require more subtle diagnostic and clinical acumen.

In the most widely used diagnostic system, ovulatory disorders are classified in three broad categories based on clinical and laboratory evidence of ovarian estrogen production and serum gonadotropin levels.

1. Patients in Group l are collectively designated as having hypothalamic-induced anovulation. These women present with low estrogen levels coupled with low gonadotropin levels. Common causes of hypothalamic dysfunction include excessive exercise and competitive sports, psychogenic weight loss including anorexia nervosa and bulimia, as well as anxiety and other forms of emotional stress.
2. Patients in Group ll characteristically have increased or normal endogenous estrogen production and gonadotrophin levels within the normal range. Polycystic ovarian syndrome account for the vast majority of patients in group ll. More about Polycystic Ovarian Syndrome
3. Patients in Group lll present with menstrual and ovulatory disorders coupled with menopausal estrogen level and elevated gonadotropins. This group includes patients with premature ovarian failure and other causes of gonadal failure.

 
As stated above, patients presenting with a history of infrequent, irregular menstrual cycles should be considered anovulatory. A past history of regular menses followed by the abrupt onset of amenorrhea may suggest the presence of some organic disorder such as a hormone-producing tumor. This is particularly true when this change is not accompanied by significant changes in weight. The initial interview should elicit any history of pituitary, thyroid, or adrenal disease or whether the patient has noted any galactorrhea or symptoms of androgen excess. Laboratory and clinical assessment including include determination of endogenous estradiol and gonadotropin levels as well as serum or urine pregnancy testing. Most patients can be correctly classified into the correct diagnostic group without additional invasive testing. In rare cases the diagnosis may require the use of ultrasound, pituitary or hypothalamic imaging and rarely laparoscopy.

Read Part Two of this article to learn review available treatment option for ovulatory dysfunction