Polycystic Ovarian Syndrome / Infertility
What is Polycystic Ovarian Syndrome (PCOS)?
PCOS is a disorder caused by elevated insulin levels stimulating the ovary to make excessive amounts of male hormone. Excessive amounts of male hormone can result in late or complete lack of ovulation. Because of hyperandrogenemia and insulin resistance it is very easy for the PCOS patient to gain weight, frequently patients are overweight. It is believed that PCOS is an inborn, genetic disorder with multiple inheritance patterns. PCOS affects approximately 10% of women. It is believed that the basic pathology is insulin resistance. With appropriate testing the majority of women with PCOS can be demonstrated to have insulin resistance. Therefore drugs that reduce insulin resistance are beneficial – the most widely used drug is metformin.
Making the diagnosis of PCOS.
The most widely agreed upon criteria for making the diagnosis of PCOS came about through agreements with the American Society for Reproductive Medicine and the European Society of Human Reproduction. To make the diagnosis of PCOS an individual must have at least two of the following three criteria: 1) oligo – or amenorrhea (late or no ovulation).
2) hyperandrogenism, either by clinical signs or laboratory findings. 3) ultrasound evidence of PCOS, i.e., multiple small peripheral follicles.
PCOS treatment for the infertility patient.
On ultrasound most PCOS patients will typically have findings of small peripheral cysts, these cystic preantral follicles contain the developing eggs that have stopped development. Development of these preantral follicles has ceased because of excessive androgen production. Without continued development of the preantral follicle a woman will not ovulate and cannot become pregnant. Treatment for the PCOS infertility focuses on restoring normal ovulation through the use of fertility medications. Medications that have been shown to be effective include antiestrogens, clomiphene citrate and letrozole, gonadotropin medications as well as medications that reduce insulin levels, metformin. In most cases an antiestrogen either clomiphene citrate or letrozole will be tried initially. Antiestrogens act by fooling the body into thinking there is no estrogen production, the body compensates by producing high levels of gonadotropins, LH and FSH (the two hormones that stimulate the follicle growth). If regular ovulatory cycles are not induced – addition of other medications can be tried, usually metformin. If a patient has persistent oligo-ovulatory or anovulatory cycles, the initial dose of antiestrogen can be increased or treatment with gonadotropins or low doses of a steroid can be tried. Gonadotropins are the strongest stimulants of growth – indeed, special care must be used with these drugs on PCOS patients so they to do not hyperstimulate, i.e., make an excessive number of follicles, potentially resulting in a serious condition known as ovarian hyperstimulation syndrome. Ideally the PCOS patient should be monitored very closely when using any ovulation induction medication to minimize the risk of multiple pregnancy as well as ovarian hyperstimulation syndrome. In very resistant individuals surgical therapy with a technique known as wedge resection or ovarian drilling can be performed. With this surgery a portion of the androgen producing tissue is removed or destroyed. This technique is very effective in restoring ovulatory cycles either alone or with hormone therapy. Surgery does have the potential to create adhesions damaging the tubes and/or ovaries.
PCOS patients and in vitro fertilization.
For PCOS patients who have failed ovulation induction therapy or may have other infertility issues that have not responded to conservative treatment – in vitro fertilization may be recommended. Extreme care, i.e., close monitoring and low doses of gonadotropin medications must be used. Again, PCOS patients are at high risk for ovarian hyperstimulation syndrome. The PCOS patient overall tends to produce a greater number of eggs than the non PCOS patient, but frequently eggs are of lower quality. If a PCOS patient has a very high response to gonadotropin stimulation frequently triggering (bring about the final maturation of the eggs) is done using a different medication, i.e., a short acting GnRH agonist, Lupron (instead of hCG). Dostinex medication prior to triggering final egg development has been shown to reduce the risks of ovarian hyperstimulation syndrome. If the PCOS patient’s estradiol and number of follicles is felt to be very excessive it is a good idea to either cancel the cycle or consider freezing all embryos as opposed to going ahead with a transfer. If the high response PCOS patient is pregnant, pregnancy itself continues to stimulate the ovary and can result in “late onset ovarian hyperstimulation syndrome”. There is evidence to suggest improved pregnancy rates with the addition of metformin to IVF cycles. For most PCOS patients once pregnancy is established metformin is discontinued. Metformin does not reduce the risk of miscarriage. If a PCOS patient is at significant risk for diabetes metformin may be continued.