Achievement of pregnancies in women with primary ovarian insufficiency using close monitoring of follicle development: case reports

Abstract

Women with primary ovarian insufficiency (POI) or premature ovarian failure (POF) display hypergonadotropic hypogonadism due to follicle dysfunction and depletion before 40 years of age. Women with POI extremely rarely ovulate and achieve pregnancy spontaneously; however, it is believed that 5%-10% of such women will conceive and deliver a child after the diagnosis is established [1,2]. Numerous treatment protocols for follicular development and ovulation induction have been tested in women with POI; however, none have approached the success rate of utilizing donor oocytes [1,3]. Thus, for couples affected by POI the only practical alternatives for having a child are adopAchievement of pregnancies in women with primary ovarian insufficiency using close monitoring of follicle development: case reports Abstract. Women with primary ovarian insufficiency (POI)/premature ovarian failure exhibit hypergonadotropic hypogonadism due to follicle dysfunction and depletion before the age of 40 years. Because ovulation is extremely rare and thought to be unpredictable in women with POI and because no ovulation induction regimens have been shown to be efficacious, oocyte donation is the only evidence-based treatment for women with POI with desired fertility. Oocyte donation is, however, extremely limited in several countries including Japan. Here, we report four women with POI who achieved pregnancies resulting from timed intercourse or intrauterine insemination in combination with cyclic estrogen/progesterone therapy and close monitoring of follicle development. These four patients were diagnosed with POI at the mean age of 27.5 ± 8.5 (mean ± SD; range, 19-35), subjected to follicle monitoring at the mean age of 29. 8 ± 5.7 (23-35), and conceived at the mean age of 34.5 ± 3.9 (29-38). The interval between the initiation of follicle monitoring and pregnancy was 4.8 ± 2.8 (2-8) years. In one of the patients, her most recent ovulation occurred after a three-year interval. All four patients had uncomplicated pregnancies with term deliveries. In the event that oocyte donation and adoption are not available and/or various treatments with intensive ovulation induction have been unsuccessful, close and continuous monitoring of follicle growth to identify very rare ovulatory events might be considered for patients with POI and desired fertility.

Prediction of Ovarian Response in Women with Premature Ovarian Insufficiency Stimulated By Gonadotrophins Using Day-3 Serum Estradiol: A Retrospective Study

“…The POI also had an inverse relationship with follicular growth and pregnancy, although a significant difference was not demonstrated, presumably due to small sample size. There are various case reports in the literature involving POI women who spontaneously and unexpectedly got pregnant [6,8,[14][15][16][17][18][19][20][21][22][23][24][25], but very few had demonstrated statistical analysis of this population due to the rarity of POI. Bidet et al [26], demonstrated predictive factors for spontaneous recovery of ovarian function in POI women.…”

Serum estradiol level during withdrawal bleeding as a predictive factor for intermittent ovarian function in women with primary ovarian insufficiency

“…Both of these options, however, are extremely limited in Japan due to ethical problems [24]. We previously reported 4 women with POI who conceived by timed intercourse (TI) or intrauterine insemination (IUI) in combination with close monitoring of follicle growth [25]. All the patients gave birth to healthy babies with an uncomplicated perinatal course.…”

“…None of the patients had male factor infertility or a history of pelvic radiotherapy. Four of the 25 patients who gave birth to healthy babies were described previously [25]. Clinical, ultrasound, and endocrine evaluations, and karyotype determinations were performed.…”

“…As previously described [25], patients with POI desiring pregnancy with their own oocytes provided a semen specimen from their partner for analysis and underwent hysterosalpingography to rule out other causes of infertility. They were then most often treated with cyclic hormone therapy (cyclic EPT) using estrogen (conjugated equine estrogen [CEE], 1.25 -2.5 mg [Premarin®, 2 -4 tablets]/day for 7 -28 days, representing an absolute time period) followed by estrogen in combination with progestin (0.5 mg norgestrel and 0.05 mg ethinylestradiol [Planovar®, 1 tablet] or 2.00 mg chlormadinone acetate and 0.05 mg mestranol [Lutedion®, 1 tablet]/day for 10 -12 days, representing an absolute time period), or in some occasions, human menopausal gonadotropins with or without estrogen or gonadotropin-releasing hormone agonist.…”

Association between spontaneous ovulation and serum anti‐Müllerian hormone levels in a premature ovarian insufficiency patient after a multimodal treatment for breast cancer

“…It is common during the different types of cancer treatments that female adolescents and young adult (AYA) patients with cancer experience premature ovarian insufficiency (POI) due to the high toxicity of chemotherapy damaging the patient's gonadal function . However, there are several case reports in the literature involving POI patients who conceived during long‐term follow‐ups . Here, we report the case of an AYA patient suffering from POI after multimodal breast cancer treatment.…”