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    Poor Ovarian Response

    One of the most difficult problems in IVF today is what we call “poor ovarian response”.  In that case, a patient on medication for ovarian stimulation and oocyte production doesn’t respond as expected and produces too few or no oocytes at all.

    Pregnancy achievement rates following IVF are known to be directly related to the number and quality of embryos transferred. The more oocytes a patient produces during ovarian stimulation, the more embryos may be created. The best among them – i.e. those with the best potential for pregnancy achievement – are selected and transferred.

    For that reason, patients who respond well to ovarian stimulation and produce sufficient oocytes finally have better chances of achieving pregnancy.
    Usually, ovarian function is observed to depend on age: as women age, ovarian response is reduced. Every girl is born with a large number of oocytes in her ovaries, gradually diminishing though as the woman ages (i.e. ovarian reserve is reduced). The reproduction gynaecologist is rather interested in the patient’s “biological age” – i.e. ovarian function and number of remaining oocytes – than in her calendar age.
    One way to control ovarian reserve is via a blood test. On the 2nd day of the menstrual cycle, we check follicle stimulating hormone (FSH) levels. If they are increased, they indicate low ovarian reserve, while if they are too high (exceeding 20 mIU/ml), ovarian deficiency is diagnosed (the ovaries don’t function normally). High FSH levels do not mean that a woman cannot get pregnant, certainly though chances of achieving pregnancy are reduced, because low quality oocytes are produced.
    Why are FSH levels increased in women with limited ovarian function? FSH is produced by a gland in the brain called hypophysis, and is responsible for oocyte maturation in the ovary every month. In young women with many high quality oocytes, even low FSH levels are sufficient for oocyte development. In older women, with less and lower quality oocytes, the hypophysis must produce more FSH to enable oocyte maturation.
    It would also be useful to check the FSH/LH (luteinizing hormone) ratio. Normal FSH/LH ratio is 1. If the FSH rate is much higher than the LH rate, this indicates low ovarian reserve.
    Another hormone called estradiol (Ε2) must also be checked on the 2nd day of the menstrual cycle, along with FSH. If E2 levels are high, they may reduce FSH to normal rates, thus misleadingly showing that FSH levels are normal. High E2 rates indicate low oocyte reserve in the ovaries. 
    Another test used lately tests the levels of two more hormones (inhibin B and AMH, Anti-Mullerian Hormone) in the blood. Low inhibin B and AMH levels (produced by good quality oocytes) indicate low ovarian reserve.
    However, even if a test shows normal FSH levels, this doesn’t mean that oocyte quality or number will be sufficient. For that reason, a very useful way to diagnose ovarian status is consider the patient’s medical history and evaluate her response to an ovarian stimulation she may have had in the past.
    Besides laboratory tests for the evaluation of ovarian status and function, clinical examination is also required. Ovaries and follicles are depicted with an ultrasonogram. The most useful test counts the number of immature follicles in the ovary on the 3rd day of the menstrual cycle. Follicles are counted by means of a transvaginal ultrasound. Immature follicles are small in diameter (usually 2-8mm). Their number is directly related to ovarian response to stimulation. A normal number of immature follicles counted varies between 15 and 30. If immature follicles are less than 6, the prognosis is poor.
    Ovarian volume (size) is also indicative of ovarian response. Normally, the total volume of both ovaries reaches 10 ml approximately. Patients with small ovaries (volume of less than 4 ml) show poor response.
    Older women are often prepared for a possible deficient response of their ovaries to stimulation. If this happens to a younger woman though, it certainly is quite difficult for her to accept it and deal with it. Most young women expect to have plenty of good quality oocytes, exactly because they are young and have a regular menstrual cycle. Unfortunately sometimes things might be different. When a woman has regular menstrual cycles, this means that her oocytes are sufficiently good to trigger hormone production and menstruation – but not necessarily to enable pregnancy.
    In every woman, oocyte quality and quantity may be nomal for her age (around average), but it also may be better or worse than average. We say that women with low quality oocytes have low ovarian reserve or low ovarian function.
    Medical books claim that there is no treatment for high FSH levels. When oocytes run out, ovaries cannot produce new ones.
    We must remember though that high FSH rates are not the cause of infertility, but only an indicator of poor oocyte quality. Thus, the effort to treat high FSH rates is meaningless and won’t help achieve a pregnancy.  
    Many therapeutic strategies have been developed for patients with poor ovarian response. Since time is critical for them, treatment must be aggressive, in order for pregnancy to be achieved before ovarian reserve is exhausted. IVF is the best choice, because it offers the highest success rates. Ovarian stimulation in those patients is quite difficult, so the doctor’s experience and skills are decisive. No matter how well coordinated the doctor’s attempt is, unfortunately, there still are significant odds of failing.
    What happens if you are young, but suddenly, during your first IVF cycle, you are diagnosed with poor ovarian response? This is a really difficult problem, because on the one hand this is unexpected and on the other hand the patient isn’t psychologically and emotionally prepared to deal with it. In that case, there are the following options: to continue the cycle, increasing the medication dosage, or to stop the cycle and repeat the treatment later on, in a new cycle, after having increased the medication dosage. However, the prognosis remains poor and there is no guarantee that increased drug dose will yield more oocytes.
    The option with the highest pregnancy achievement rates for patients with poor ovarian response is oocyte donation. From a medical point of view, oocyte donation is a simple technique; it may be psychologically or emotionally difficult though for a woman (or couple) to make that choice.
    Most of the times, it is worth trying an IVF cycle with the patient’s own oocytes, even if statistically, there are few chances of achieving pregnancy. In a number of cases, women with such problems have succeeded to conceive, even with only 2-3 oocytes produced and only one (1) embryo transferred.
    However, even if the cycle fails, the couple knows that everything possible has been done and prepares psychologically and emotionally to calmly explore other options (oocyte donation, adoption), so as to create the family of their dreams.

    Gennima | Gynaecology & Reproduction Center

    346 Kifisias Avenue, 15233 Chalandri - Athens, Hellas
    +30 210 68 16 100
    +30 210 68 30 321 (fax)