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Case Reports
. 2017 Sep 20;17(1):312.
doi: 10.1186/s12884-017-1510-6.

Successful pregnancy and live birth from a hypogonadotropic hypogonadism woman with low serum estradiol concentrations despite numerous oocyte maturations: a case report

Kaori Matsumoto  1 , Kazuhiko Imakawa  2 , Chuyu Hayashi  3
Affiliations
Case Reports

Successful pregnancy and live birth from a hypogonadotropic hypogonadism woman with low serum estradiol concentrations despite numerous oocyte maturations: a case report

Kaori Matsumoto et al. BMC Pregnancy Childbirth. .

Abstract

Background: The increase in serum estradiol (E2) concentrations during the follicular phase becomes the index of oocyte maturation in vivo. When ovarian stimulation is performed to hypogonadotropic hypogonadism (HH) patients with only follicle stimulating hormone (FSH), proper increase in serum E2 concentrations is not observed. Even if oocytes are obtained, which usually have low fertilization rate. In this report, we would like to present an unique case, in which under low E2 concentrations and without luteinizing hormone (LH) administration, numerous mature oocytes could be obtained and a healthy baby delivered.

Case presentation: During controlled ovarian stimulation (COS) with only recombinant follicular stimulating hormone (rFSH) administrations, a 26-year-old Japanese woman with hypothalamic amenorrhea (i.e., hypogonadotropic hypogonadism) developed numerous follicles despite low serum E2, 701 pg/ml, and high progesterone (P4) concentrations, 2.11 ng/ml, on the day of induced ovulation. However, 33 cumulus-oocyte complexes (COCs) were successfully obtained; following the embryo culture, four early embryos and six blastocysts were cryopreserved. This patient received hormone replacement therapy (HRT), during which one of six cryopreserved blastocysts was thawed and transferred into the uterine lumen. The patient became pregnant from the first transfer, went through her pregnancy without any complications, and delivered a healthy male baby in the 39th week. Low E2 concentrations in follicular fluids (FFs) are suggestive that aromatase and/or 17β-hydroxysteroid dehydrogenase (17β-HSD) could be low.

Conclusions: Serum E2 concentrations may not be the most important index for oocyte maturation during COS, and suggested that oocyte maturation was in progress even under low serum E2 and high P4 conditions. Even if serum E2 concentrations did not properly increase, numerous mature oocytes could be obtained, resulting in the birth of a healthy baby.

Keywords: Assisted reproductive technology; Controlled ovarian stimulation; Follicular fluids; High progesterone; Hypogonadotropic hypogonadism; Hypothalamic amenorrhea; Low estradiol; Luteinizing hormone.

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Written informed consent was obtained from the patient for publication of this case report and any images and clinical data. A copy of the written consent is available for reviewer by the editor of this journal.

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All the author’s declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Follicular development following controlled ovarian stimulation (COS). Ovarian response was monitored through the use of transvaginal ultrasonography during COS. During the first COS, measurable follicles were not observed in either ovary on day 3 of the menstrual cycle (MC). On the same day, COS was initiated with daily administration of 225 international unit (IU) recombinant follicle stimulating hormone (rFSH). Follicular development and increased progesterone (P4) concentrations were observed, but estradiol (E2) concentrations were low on day 11. Although the right (R) and left (L) ovaries had over 30 follicles of 15–19 mm on day 13, serum E2 concentrations were low at 484 pg/ml and P4 concentrations were high at 2.09 ng/ml. COS was canceled due to the hormone concentration which did not reflect those of numerous follicular developments. From the day when the first COS was canceled, the patient took 10 mg synthetic progesterone (SP) orally for the next 14 days. The patient experienced withdrawal bleeding, and several small follicles were observed in both ovaries on day 3. From the same day, the daily dosage of 175 IU rFSH was administered for the first 5 days, followed by 200 IU for the remaining treatment period. Similar to the response seen at the first COS, high serum P4 concentrations, 2.11 ng/ml, were observed; however, serum E2 concentrations, 701 pg/ml, did not reflect those of numerous follicular developments
Fig. 2
Fig. 2
Comparison of steroid hormone concentrations of this patient to those of infertile patients (Inf-), Inf-A and Inf-B. On day 4 of the menstrual cycle, these infertile women received daily administration of 100 mg clomifene citrate (CC) for 5 days. Follicular diameters were 25.2 mm and 18.1 mm for Inf-A and 22.8 mm for Inf-B on the day of induced ovulation. From the same day, serum hormone concentrations for Inf-A and Inf-B were 692 pg/ml and 745 pg/ml E2, 10.5 mIU/ml and 8.0 mIU/ml LH, and 0.40 ng/ml and 0.29 ng/ml P4, respectively. Ovulation was induced with 600 μg gonadotropin releasing hormone (GnRH) agonist, followed by oocyte pick-up (OPU), in vitro fertilization (IVF) and follicular fluids (FFs) cryopreservation in the same manner. However, no oocyte was collected from Inf-A, while one oocyte was collected from Inf-B, but its development ceased after fertilization. Although progesterone (P4), dehydroepiandrosterone sulfate (DHEA-S) and androstenedione (A2) concentrations in FFs of this patient did not differ from those of Inf-A and Inf-B, estrone (E1), testosterone (T) and estradiol (E2) concentrations were lower than those of Inf-A and Inf-B
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