Premature ovarian insufficiency can reverse temporarily with ovulation
A 2014 review by one author reports that ovulation occurred in about 2 out of 10 attempted cycles after high FSH was lowered in 100 women with early ovarian failure. It also cites case reports and randomized trials.
Nearly 4 in 10 women with premature ovarian insufficiency ovulated in the case series. Source: Check JH, 2014, PMID 24848073.Study at a glance, case series of 100 consecutive women: Premature ovarian insufficiency can reverse temporarily with ovulation. Source: Check JH, 2014, PMID 24848073.
Key Findings
In 100 consecutive women with hypergonadotropic amenorrhea and estrogen deficiency, ovulation occurred in approximately 20% of attempted cycles. Overall, 37% of the women ovulated.
Among 91 women on the estrogen-hMG method, 19 conceived (20.8%). Of the 34 women made to ovulate, 19 conceived (56%). The paper reports a 50% miscarriage rate in the series.
The 1984 report of the method treated 5 patients. Three responded, and 2 of them delivered live babies.
A placebo-controlled randomized trial found ovulation in 3 of 15 women on a GnRH agonist (20%) and in none of 15 controls. The trial lacked the power to make this difference significant.
Among lymphoma patients treated with alkylating agents, 34% developed premature ovarian insufficiency, against 3% of those treated without alkylating agents.
Interpretation
This narrative review describes one author's clinical experience treating premature ovarian failure. A case series of 100 women with high FSH and low estrogen forms the core evidence, along with case reports and a placebo-controlled randomized trial testing a GnRH agonist. In the case series, 37% of the women ovulated. Lowering FSH produced ovulation in about 20% of attempted cycles. Pregnancies and live births followed in several of the women who ovulated. The author notes that spontaneous ovulation from chance alone is uncommon in women who have missed periods for years, which supports a link between treatment and the ovulation that followed. The findings support larger studies of this approach.
RRM Context
Restorative reproductive medicine asks why ovulation stopped and works with the woman's own hormonal signals. The review applies that aim to premature ovarian insufficiency and to a woman's own eggs. The reviews it quotes offer donor eggs or adoption. Protocols differ among clinicians and are not described here. Excision by a skilled surgeon is the surgical standard for endometriosis.
Our editorial summary of this paper, not the article's abstract.
Abstract
Premature ovarian insufficiency, defined as amenorrhea with estrogen deficiency in a woman younger than 40 associated with a serum follicle stimulating hormone (FSH) >35 mIU/mL, can be temporarily reversed with ovulation achieved resulting in live delivered pregnancies. Though this may occur spontaneously the frequency of ovulation can be considerably increased by various techniques of lowering the elevated serum FSH level and thus up-regulate down-regulated FSH receptors in the granulosa-theca cells. This can be accomplished by either suppressing FSH release from the pituitary by negative feedback through high dose estrogen or by suppressing FSH production by inhibiting the gonadotropin releasing hormone (GnRH) by either using GnRH agonists or antagonists. The estrogen method is the technique of choice because it is much less expensive than GnRH analogues, and helps stimulate cervical mucus and endometrial development. Ethinyl estradiol is the preferred estrogen because it does not contribute to the measurement of serum estradiol and thus allows proper monitoring of follicular maturation. Sometimes exogenous gonadotropins are needed as a boost but the dosage should be low so as not to down-regulate FSH receptors again. The technique is referred to as the FSH receptor restoration technique. Progesterone should be supplemented in the luteal phase. Physicians should be cognizant of trying to help prevent premature ovarian insufficiency by judiciously choosing less gonadotoxic cancer treatment alternatives that are equally efficacious. Also surgery for ovarian endometriomas should be performed only when absolutely necessary.
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