Female review


Introduction

Of the female causes of infertility, the most common is ovulatory, which is found in 15-25% of couples presenting with fertility issues (1). Chronological age, while important, is not as critical a determinant of female fertility as ovarian function. Disorders in ovulation are not only the most common, but they are also the most important to recognise, since the majority of these conditions, if diagnosed early, may be treated successfully so as to achieve a pregnancy. The critical importance of FSH levels has been acknowledged in various for a, including the XVI World Congress of Fertility and Sterility 1998 (a joint meeting of the American Society for Reproductive Medicine (ASRM) and the International Federation of Fertility Societies)(2), as well as in other recent literature (3).

At the XVI World Congress of Fertility and Sterility, it was acknowledged that “female age is the main determinant of the outcome of fertility treatment, [but] the effect is almost entirely ovarian in origin”. (4) Hull elaborates on this observation by stating that “the FSH level to be a more important independent determinant of ovarian responsiveness than age” and that consequently, “measurement of basal FSH levels in infertile women is prognostically valuable”. (5)


Day 3 FSH as a screen for female subfertility

Day 3 FSH is used extensively worldwide to assess ovarian function, and there is a large body of literature that supports the established relationship between Day 3 FSH level and ovarian responsiveness (6).


It is widely acknowledged that infertility increases with a woman’s age. Women are born with a finite number (about 400,000) of eggs. When a woman of 40 ovulates, the egg she releases is 40 years old. Due to chromosomal abnormalities that increase with age, these older eggs have a lower likelihood of fertilising successfully. Natural fecundity (the monthly chance of conception) in women peaks at the age of 25 years, and declines gradually after the age of 30 years. The decline accelerates at around 35 years and reaches almost zero by the age of 45. (7).

However, there is a great deal of variability in each patient. This process of oocyte deterioration can start very early in some patients and later in others.

In concert with the decline in natural fecundity seen in women starting at approximately 30 years of age, FSH levels have also been shown to increase throughout this period. For example, Ahmed Ebbiary and colleagues observed a statistically significant and progressive increase in FSH levels in a population of 500 regularly cycling subfertile women as early as 29-30 years of age (8). Moreover, elevated FSH levels in younger women are likely to indicate fertility problems. In a published paper by Tourt and Seifer, it was reported that women with unexplained recurrent pregnancy loss had statistically significantly higher day 3 FSH values than women for whom the cause for their recurrent pregnancy loss is known (9). To test whether elevated day 3 FSH occurred only in women >34 years old, these authors reviewed the ages of women with elevated day 3 FSH and unexplained recurrent pregnancy loss and found that if they had only measured this hormone in older women, they would have missed 24% of the women who had elevated values. These results led the author to conclude that “it therefore seems prudent to test for diminished ovarian reserve in all women who present for evaluation of recurrent pregnancy loss” (10).

Data from IVF studies support the predictive value and clinical utility of measuring day 3 FSH in younger women with fertility problems. Hull reports substantially reduced implantation rates following UVF for oocytes from younger women who have elevated basal FSH levels (11). He concludes, as noted above, that these data support “the routine use of basal FSH measurement in the investigation of fertility”.

Bibliography

  1. American Society for Reproductive Medicine. 2000. Fact Sheet: Infertility.
    www.asrm.org/Patients/FactSheets/infertility.html
  2. Templeton, A. 1998, Age and Fertility. Proceedings of the XVI World Congress on Fertility and Sterility. Pp 157-65
  3. See e.g Hull, M.G.R. 1995. Female age and fecundity. Proceedings of the 15th World congress on Fertility and Sterility. Eds. Hedon,b., et al. Parthenon Publishing 1995
  4. See supra note 2
  5. See supra note 3
  6. See.e.g, Sharara, F.I., et al. 1998. The detection of diminished ovarian reserve in infertile women, American Journal of Obstetrics and Gynecology 179:804-12; Toner, J.R., et al. 1991. Basal Follicle stimulating hormone level is a better predictor of IVF performance than age. Fertility and Sterility 55:784-91; Oosterhuis, G.J.E., et al. 1998. Follicle stimulating hormone measured in unextracted urine: a reliable tool for easy assessment of ovarian capacity. Fertility and Sterility 70:544-8; Seifer, D.B., et al. 1996. Apoptosis as a function of ovarian reserve in women undergoing IVF. Fertility and Sterility 66:593-8; Hull, M.G.R. 1995. Female age and fecundity. Procedings of the 15th World congress on Fertility and Sterility. Eds. Hedon,B., et al. Parthenon Publishing, 1995; Magarelli, P.C., et al. 1996 Discrimination between chronological and ovarian age in infertile women aged 35 years and older: predicting pregnancy using basal follicle stimulating hormone, age and number of ovulation induction / intra uterine insemination cycles. Human Reproduction 11:1214-19
  7. Hull, M.G.R. 1995. Female age and fecundity. Proceedings of the 15th World congress on Fertility and Sterility. IFFS-95(22):181
  8. Ahmad Ebbiary, N.A., et al., 1994. Hypothalamic - pituitary ageing: progressive increase in FSH and LH concentrations throughout the reproductive life in regularly menstruating women. Clinical Endocrinology 41:199-206
  9. Trout, S.W., and Seifer, D.B., 2000. Do women with unexplained recurrent pregnancy loss have higher day 3 serum FSH and estradiol values? Fertility and Sterility 74(2):335-7
  10. Id at 337
  11. See supra note 3