Spontaneous pregnancy fifteen years after diagnosis of premature ovarian failure

A Wijesiriwardana 1, A Shetty2

Corresponding address – 

1Department of Obstetrics and Gynaecology, Cumberland Infirmary, Newtown Rd, Carlisle, Cumbria, CA2 7HY, UK 

2Department of Obstetrics, Aberdeen Maternity Hospital, Foresterhill, Aberdeen, AB25 2ZD, UK.

SMJ 2007 52(2): 56

 

Abstract

We report an unusual case of spontaneous conception, occurring over fifteen years after the initial diagnosis of premature ovarian failure (POF). Her karyotype was 46XX. Following the diagnosis of POF, our patient was treated with hormone replacement therapy (HRT). Starting at the age of 31, she had several invitro fertilisation (IVF) cycles using donor eggs. She had two live births and one ectopic pregnancy for which she underwent laparoscopic salpingectomy. Between IVF treatment cycles she continued HRT. At the age of forty years she conceived spontaneously. The HRT was stopped at 10 weeks of amenorrhoea. She delivered a healthy baby boy at term. Following the delivery the patient had spontaneous periods every 2-3 months and did not suffer from menopausal symptoms. Her post delivery FSH and LH levels were high. We believe this is the longest interval reported between diagnosis of POF and a spontaneous conception. 

Keywords – premature ovarian failure, spontaneous pregnancy

 

 

We report an unusual case of spontaneous conception, occurring many years after the initial diagnosis of premature ovarian failure (POF).

 

A 29-year-old woman was seen at the gynaecology clinic with symptoms of hot flushes and excessive sweating over the previous four years.  Her menarche was at 15 years of age and she had commenced the oral contraceptive pill soon after. On stopping the pill aged 25 years, she experienced unbearable hot flushes and sweating and thus recommenced the combined pill almost immediately.  She had not had a period outside of that induced hormonally for several years.  On examination, she had normal secondary sexual characteristics.  The investigations at the clinic were consistent with the diagnosis of premature ovarian failure  (LH 23.3 u/l, FSH 112.9 u/l, prolactin 268 u/l oestradiol 121 nmol/l).  Her karyotype was 46XX.

 

Following the diagnosis of POF, our patient, was treated with hormone replacement therapy (cyclical oestrogen and progesterone).

 

At 31 years of age, the patient had an unsuccessful embryo transfer following invitro fertilisation (IVF) with oocytes donated by her sister.  The following year she achieved a successful pregnancy following IVF using anonymous donor eggs and had a baby boy delivered vaginally, at term.  She had two further unsuccessful attempts of assisted reproduction with donor eggs in 1996.  The first attempt resulted in an ectopic pregnancy, for which she underwent laparoscopic salpingectomy.  In 1998 she had two further unsuccessful embryo transfers, with nine embryos frozen for future use.  In 1999, all the remaining embryos were thawed and three of the best embryos transferred.  This was successful attempt and she delivered a baby girl at term.  Between IVF treatment cycles she continued hormone replacement and her menstrual cycle pattern remained regular on this. 

 

In 2001, over 15 years after the initial diagnosis of premature menopause our patient, conceived spontaneously.  The HRT was stopped at 10 weeks gestation when the pregnancy was diagnosed.  The pregnancy proceeded without problems and she delivered a healthy baby boy at term.  Following the last delivery our patient, had spontaneous periods every 2-3 months and did not suffer from vasomotor symptoms.  Her post delivery FSH, LH was 46.9 u/l and 26.8 u/l respectively.  Her luteal phase progesterone levels were less than 0.6 nmol/l, suggesting anovulatory cycles.  She was, however advised to use some form of contraception as she did not wish further pregnancies. 

 

Discussion

Amenorrhoea, elevated gonadotrophins and oestrogen deficiency occurring before the age of forty is considered, by definition, to be premature ovarian failure.  Coulam et al estimated the incidence of POF to be about 1% of all women during the reproductive years.1

 

While normal menopause is generally an irreversible condition, POF is characterised by intermittent ovarian function in half of these young women, with intermittent oestrogen production and even ovulation despite the presence of high gonadatrophin levels.2  Some women with spontaneous POF have been found to possess apparently normal primordial follicles.3   Spontaneous conception is possible with a lifetime chance of this occurring quoted at around 10-15 %.4

 

Various therapies have been used in an attempt to induce fertility, including sex steroids and gonadatrophin-releasing hormone agonists to suppress circulating gonadatrophin. POF is frequently associated with autoimmune conditions.  Corticosteroids have been used to overcome autoimmunity.  These have failed to demonstrate any significant improvement in ovulation and pregnancy rates.  In vitro fertilisation using donor oocytes have demonstrated high pregnancy rates in women with premature ovarian failure.5  Donor oocyte in vitro fertilisation-embryo transfer success rates were not different in women with or without POF suggesting uterine receptivity in such women is unimpaired.6 It has been observed that women who have a previous successful pregnancy following oocyte donation are highly likely to conceive spontaneously in a subsequent cycle7, as seen in this patient.

 

We believe that this case is the longest interval reported, between the spontaneous onset of POF and spontaneous conception.  Previous cases have reported intervals of 1-8 years between POF and conception spontaneously.8, 9, 10  This case becomes even more interesting as the clinical features of the menopause improved following the last spontaneous conception as in the case reported by Zargar et al.11  They speculated about the possibility of elevated gonadotrophins causing down regulation of gonadatrophin receptors and restoration of the sensitivity of the few remaining ovarian follicles by lowering of serum gonadotrophins with oestrogen therapy.  In this patient, there was improvement of menopausal symptoms with gonadatrophin levels remaining elevated, although the FSH levels did seem to be lower than at initial diagnosis.

 

References

  1. Coulam CB, Adamson SC, Annegers JF, Incidence of premature ovarian failure.  Obstet Gynaecol 1986; 67: 604-6 

  2. Nelson L.M, J.N Anasti, L.M Kimzey et al. Development of luteinized graafian follicles in patients with karyotypically normal spontaneous premature ovarian failure. J Clin. Endocrinol.Metab 1994;79:1470-1475 

  3. Rebar RW, Erickson GF, Yen SSC, Idiopathic premature ovarian failure, clinical and endocrine characteristics. Fertil Steril 1982; 37:35-41 

  4. O’Herlihy C, Pepperell RJ, Evans JS, The significance of FSH elevation in young women with disorders of ovulation. Br Med K 1980; 281: 1447-1450 

  5. Morris RS, Sauer MV, New advances in treatment of infertility in women with ovarian failure. Curr. Opin in Obstet. Gynecol. 5(3);368-77, 1993. 

  6. Lydic ML, Liu JH, Rebar RW, Thomas MA, Cedars MI, Success of donor oocyte in in-vitro fertilization-embryo transfer in recipients with and without premature ovarian failure.  Fertil Steril.65(1);98-102,1996. 

  7. Edwards R.G, Why are agonadal and post-amenorrhoeic women so fertile after oocyte donation? Hum. Reprod. 1992;7: 733-734 

  8. Fang-Ping Chen, Shiu-Young Chang, Spontaneous pregnancy in patients with premature ovarian failure, Acta Obstet Gynecol Scand 1997; 76: 81-82 

  9. Chao SL, Huang LW, Yen HR. Pregnancy in premature ovarian failure after therapy using Chinese herbal medicine, Chang Gung Medical Journal. 26(6); 449-52, 2003 

  10. Menashe Y, Pearlstone AC, Surrey ES.  Spontaneous pregnancies despite failed attempted at ovulation induction in a woman with iatrogenic premature ovarian failure. J. Prego Med. 41(3);207-10. 1996

  11. Zagar AH, Salahuddin M, Wani Al, Bashir MI, Masoodi SR, Laway BA. Pregnancy in premature ovarian failure; a possible role of oestrogen plus progesterone treatment, Journal of the Association of Physicians of India. 48(2);213-5, 2000

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