Successful IVF pregnancy in a case of Adolescent Idiopathic premature ovarian failure.

Dr Charu Johari; Consultant Gynaecologist and IVF specialist, Indira IVF, Alwar.

Key words: In Vitro Fertilization (IVF), premature ovarian failure (POF), adolescent, IVF, HRT, Donor oocyte.

Introduction: 

Premature ovarian failure is cessation of menses before 40 years of age because of depletion or dysfunction of ovarian follicles. The average age of menopause is 50 years.¹ Adolescent idiopathic premature ovarian failure is rare, and the incidence is estimated around 1 in 10,000 in women less than 30 years.(2) 

Case report:

The patient was 24 years old and was a diagnosed case of premature ovarian failure. Because of non-development of secondary sexual characteristics and primary amenorrhea, at age of 15 years patient visited to gynecologist and further referred to endocrinologist. There was no history of any genetic etiology. At that time as documented during physical examination breast development was tanner stage 1, pubic hair were tanner stage 1 and axillary hair were absent. Patient was evaluated and her hormones thyroid profile, serum testosterone, Dehydroepiandrosterone, serum prolactin was normal, TPO antibodies were absent. Her karyotyping was normal (46xx). Her serum FSH was 0.5mIU/ml at age of 15 years, 14.23mIU/ml at age of 16 years and 97mIU/ml at age of 18 years ,FSH was repeated after one month which was 98 Miu/ml. E2 value was <20pg/ml. At fifteen years her ultrasound showed uterus size 32x18x16 mm with bilateral streak ovaries.  She was started with cyclical estrogen and progesterone. With the hormone therapy her breast development started, and her uterus size also increased. As patient and her family were aware and were in regular follow-up under endocrinologist, patient was referred to us by endocrinologist for fertility management after two years of married life. The patient was phenotypically normal, with height 168-centimeter, body mass index 22.4 kg/m², breast tanner stage 4, pubic hair tanner stage 4 and axillary hair were present. The marriage was nonconsanguineous. In pedigree evaluation neither birth defect nor genetic disorder was found in the family. Husband’s semen analysis showed normal count and motility. On 20^th day of her oral contraceptive pill cycle, uterus was 6.0 x2.8x 5.3 centimeter in size with homogenous endometrium of 5.1mm in thickness. Bilateral ovaries were atrophic with no follicular activity. Thyroid and prolactin hormones were normal and antimullerian hormone was< 0.01 ng/ml.

 Patient was counselled and the need of donor oocytes explained to the patient. The couple agreed for IVF with donor oocytes. A suitable donor was screened for infectious and hereditary diseases and stimulated with Human menopausal gonadotrophins (Gynogen 225 IU) using antagonist protocols for 11 days. The oocytes were retrieved after 36 h of GnRH agonist trigger. Using husband’s sperm, ICSI was done.  Endometrial preparation was done with estradiol valerate. Two embryos were transferred on blastocyst stage after laser assisted hatching. Pregnancy was confirmed with serum beta human chorionic gonadotropin β-hCG hormone. Trans vaginal ultrasound done at 6 weeks gestational age showed a dichorionic diamniotic twin pregnancy. Nuchal translucency at 12 wks of gestation were 2.4 mm and 2.2 mm for both fetuses respectively. Aneuploidy screening at 13 weeks with non invasive prenatal screening test was normal. Pregnancy went uneventfull and she delivered a female child at 36 wks of pregnancy without any perioperative complications.

Discussion:

Idiopathic POF is an uncommon diagnosis in the adult population, even less common in the adolescent population, and little is known about its risk factors and causes. Idiopathic POF in an adolescent is rare and the incidence is not known. In an estimate it is suggested that the incidence for women less than 30 years is 1 in 10,000(2)

The presentation of POF may vary from oligomenorrhea, primary amenorrhea to secondary amenorrhea. In a study conducted in Gynecology clinic of Royal Children’s Hospital, Melbourne, seventeen patients with non-chromosomal, non-iatrogenic POF were identified between 1990 and 2006. The average age at the time of diagnosis was 16.1 years. Out of these 58.8% (10/17) presented with primary amenorrhea, 23.5% (4/17) with secondary amenorrhea and 17.6% (3/17) with oligomenorrhea(2) 

The cause of idiopathic POF may be involvement of yet unknown mechanisms which affect the rate of oocyte apoptosis. This may result a reduced complement of oocytes in the ovaries at birth or accelerated atresia. As there is no consensus to diagnose primary ovarian failure in adolescents, usually there is delay in diagnosis. Counselling of patients and their family is important regarding patient’s condition on future fertility and the risk of comorbidities associated with this condition. In our case the age of presentation was at 15 years, and the presenting complaint was non development of secondary sexual characteristics along with primary amenorrhea. 

In young females the potential causes for amenorrhea are pregnancy, polycystic ovarian syndrome, hypothalamic amenorrhea, thyroid abnormalities, hyperprolactinemia and primary ovarian insufficiency. The parents and adolescent may show different emotions ranging from apathy or denial to remorse or sadness. The health care worker who has diagnosed the case should understand the sensitive nature of the situation as well as cultural significance of the situation in the family. Impaired self-esteem and emotional distress have been reported after diagnosis of primary ovarian insufficiency and if required psychologic counseling also should be offered. It is important to start evaluation early to make a proper diagnosis .Once the diagnosis is made ,it is important to evaluate patient annually as there are other needs also and certain comorbidities  associated. The patient and her family members should be counseled regarding patient’s condition on future fertility. When desired by the patient and her family referrals to an infertility specialist and a reproductive endocrinologist should be made to discuss available reproductive treatment measures. As in our case the patient was already evaluated for absence of secondary sexual characters and primary amenorrhea, patient reached to us timely for fertility management.

 In cases of POF because of occasional spontaneous resumption of ovarian function, there is 5 % to 10% chances of natural conception. However resumption of fertility is unpredictable and there is no treatment to improve the spontaneous conception. IVF with oocyte donation has shown high success rate and is the treatment of choice in such scenario.

Women with premature ovarian failure may require multiple consecutive IVF cycles to achieve successful pregnancy. Pregnancy and live birth rates largely depend on the female’s age at time of IVF. In our case as patient was already on hormonal treatment, we could start treatment earlier. As in cases where uterus size is small, hormonal treatment to increase the size of uterus will take a further delay in treatment. 

This case highlights the importance of early diagnosis and treatment, psychological support, and the proper guidance regarding fertility so that patients can complete their family timely.