Ovarian Stimulation for IVF in Polycystic OvaryPCOS

Ovarian stimulation with gonadotropins for IVF in polycystic ovaries and/or PCOS is a particular problem and is indeed a challenge for the physician and patient. The "long" GnRH agonist-suppression protocol accompanied by pretreatment with combined oral contraceptive pills has been widely accepted as the most effective stimulation protocol for polycystic ovary/PCOS patients (Fig. 2). Pituitary suppression takes longer for polycystic ovary/PCOS patients (22). Although the optimal time to commence GnRH agonist is not clearly determined, commencement in the early follicular phase combined with oral contraceptive pills would avoid the risk of inadvertent administration during early pregnancy. The GnRH agonist protocol has been found to suppress elevated LH and androgen levels and prevent a premature LH surge, which appears to improve the pregnancy rate and reduce the miscarriage rate in PCOS patients undergoing IVF treatment (23-26).

It is very important to select the appropriate dose of gonadotropins, particularly in polycystic ovary/PCOS patients, because excessive dosage of gonadotropins increases the risk of OHSS whereas low dosage leads to poor response. Recombinant FSH products without LH are better for ovarian stimulation in patients with polycystic ovary/PCOS because of the possible deleterious effects of an excessive LH level (25,27,28).

Patients with polycystic ovaries respond the same as those with PCOS during ovarian stimulation. When comparing polycystic ovary-only women to those who had normal ovarian morphology on ultrasound examination, it was found that they produced more follicles, oocytes, and embryos, but the fertilization, cleavage, and miscarriage rates were not significantly different (9).

Hyperresponse of not only PCOS patients but also those with solely polycystic ovary morphology may be associated with increased ovarian stromal blood flow. Ovarian blood flow has been shown to be increased in both polycystic and PCOS ovaries (Fig. 3) (29). In one study women were divided into three groups: normal, polycystic ovary, and PCOS. Ultrasonographic and Doppler examinations were performed on each group on the second or third day of the menstrual cycle. Mean ovarian stromal peak systolic blood flow velocity (Vmax) in the polycystic ovary and PCOS groups was found to be significantly higher than in the normal group (16.88 cm/second and 16.89 cm/second compared with 8.74 cm/second). In addition, mean ovarian stromal time averaged maximum velocity was found to be higher in the polycystic ovary and PCOS groups and normal ovaries (10.55 cm/sec and 10.89 cm/second compared with 5.44 cm/second). However, there was no significant difference between ultrasound polycystic ovaries and PCOS. The intraovarian and uterine artery vascular differences were likely to be a result of a primary disorder within the polycystic ovary and their different hormonal status (30).

Ovarian volume, stromal volume, and stromal peak blood flow velocity are all significantly higher in the ovaries of women with polycystic ovaries and PCOS. It has been shown that there is no difference in the mean stromal echogenicity, although the stromal index is significantly greater in women with polycystic ovaries or PCOS (31).

The reason for increased blood flow is probably the increased vascular endothelial growth factor (VEGF) levels in polycystic ovary/PCOS patients. A positive correlation was observed between the serum VEGF and E2 concentrations on the day of hCG and oocyte retrieval and between the serum VEGF concentration and Doppler blood flow velocities throughout the IVF cycle (32). Serum VEGF seems to be a major capillary permeability factor in the development of OHSS ascites (33). VEGF concentrations rise after hCG administration and are higher in women who develop OHSS. Moreover, ascitic fluid obtained from OHSS patients contains high levels of VEGF, and follicular fluid VEGF concentrations are higher in women with OHSS and those with polycystic ovary/PCOS. Within ovarian and uterine blood vessels, blood flow velocities are higher both in the early follicular phase and on the day of hCG administration in women with polycystic ovary/PCOS. According to these findings, it can be concluded that there is most probably a link between VEGF, polycystic ovary/ PCOS, and OHSS.

Therefore, ovarian stimulation for polycystic ovary/PCOS in women undergoing IVF should be commenced with a smaller dose, ideally with a preparation of FSH only, and with increased ultrasound and endocrine monitoring.

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