A 27-year-old woman presents to our office to discuss her fertility. She and her husband have been trying to conceive for the past year, and she has not yet become pregnant. She reports her menses have always been irregular, coming every 30 to 90 days and lasting about 7 days. Her last menstrual period was 8 weeks ago. Although they have been actively trying for 1 year, they have not used any contraception since their wedding 2 years ago. She denies any pelvic pain or dyspareunia.
She has no past medical or surgical history. She has never used hormonal contraception and has no history of sexually transmitted infections. Her only medication is a prenatal vitamin, and she has no allergies. She has never smoked or used recreational drugs, and drinks a rare glass of wine. Her husband has never fathered any other pregnancies.
PCOS Problem and Infertility
Approximately 12% of reproductive-age women have difficulty becoming pregnant. For married reproductive-age women, there is about a 6% infertility rate. An essential component to fertility is normal ovulatory function, and ovulatory dysfunction accounts for up to 40% of female infertility. The most common cause of female infertility is PCOS problem. While evaluation for infertility is typically recommended after at least 12 months of unprotected intercourse, earlier evaluation is reasonable after 6 months of trying to conceive in women who are age 35 years and older or in those with oligomenorrhea or other evidence of anovulation.
When ovulatory dysfunction is suspected as the cause of infertility, the evaluation may be more focused. A complete menstrual history may be all that is needed to identify this cause. Ovulatory cycles are regular and predictable. They should occur about every 21-35 days with consistent flow patterns and associated symptoms. In women with oligomenorrhea, typically no specific diagnostic test is required to establish the diagnosis of anovulation. Some tests available to determine ovulation include basal body temperature monitoring, urinary luteinizing hormone detection, serum progesterone levels one week prior to anticipated cycle, or serial transvaginal ultrasounds monitoring follicular changes. It is prudent to evaluate anovulatory women for other factors contributing to infertility in a stepwise approach. Before beginning treatment, one should assess for abnormal thyroid function and hyperprolactinemia. If first-line therapies are unsuccessful in achieving pregnancy, it is recommended to check for tubal patency (via hysterosalpingogram), and male factor infertility (via semen analysis) prior to starting second-line therapies.
While not part of the diagnostic criteria, many women with PCOS problem are obese. Preconception counseling for these women should emphasize lifestyle modifications that may improve their chances of spontaneous conception. Diet, exercise, or addition of pharmacologic weight loss agents resulting in as little as a 5% reduction in body weight have been shown to improve ovulatory function. Weight loss appears to reduce circulating androgen levels and thus can lead to return of ovulation and resumption of spontaneous menses. While weight loss may help some women, many will still need ovulation induction.
Ovulation induction for women with PCOS problem can be stratified into first- and second-line treatment options.
A selective estrogen receptor-modulator has been the traditional first-line ovulation induction agent. It acts as an estrogen receptor antagonist in the hypothalamus, thus stimulating gonadotropin-releasing hormone and follicle-stimulating hormone (FSH) production, and increases circulating sex hormone binding globulin levels.
If ovulation is not achieved within 6 to 9 months of first-line therapies, it is reasonable to offer second-line therapies. Gonadotropins are an appropriate second-line therapy in women with PCOS problem who fail first-line options. Higher rates of mono-follicular development and lower risk of ovarian hyperstimulation syndrome can be achieved with low-dose regimens of gonadotropins while still achieving high rates of ovulation. Either recombinant FSH or menopausal gonadotropins (hMG) can be used with similar outcomes.
An alternative second-line therapy is laparoscopic ovarian drilling. Women who are appropriate for ovarian drilling may include those who have persistently elevated luteinizing hormone, require laparoscopic evaluation of the pelvis, or are unable to attend the intensive monitoring necessary for gonadotropins. One proposed mechanism of action is that the destruction of androgen-producing cells in the follicles and interstitial ovary leads to lower androgen and inhibin concentrations, thus allowing an increase in FSH and follicular development. Compared to gonadotropins, there are lower rates of multiple pregnancy and decreased short-term costs. Effects may be temporary and additional therapy may be necessary with clomiphene or gonadotropins. Risks include those of laparoscopic surgery such as risks of anesthesia, injury to surrounding structures, and development of pelvic adhesions.
If ovulation is not achieved with second-line therapies, the next step is just IVF. In addition, IVF becomes a reasonable option for women who achieve ovulatory cycles by any of the above mechanisms, but are unable to become pregnant after 6 to 9 cycles.
PCOS problem is the most common cause of infertility, accounting for approximately 80% of anovulatory infertility, which itself accounts for 40% of all infertility,
Infertile women with PCOS problem should be evaluated for other factors contributing to infertility by assessing for thyroid function, hyperprolactinemia, tubal patency (via hysterosalpingogram), and male factor infertility (via semen analysis),
Initial management for obese women with PCOS problem should start with lifestyle modifications, including diet and exercise,
First-line medical therapies for ovulation induction are selective estrogen receptor-modulators,
If ovulation is not achieved within 6-9 months of ovulation induction, second-line therapies, including gonadotropins or ovarian drilling, should be offered,
IVF is the final management step when ovulation does not occur with second-line therapies or pregnancy is not achieved after 6 to 9 ovulatory cycles using first- or second-line therapies.