Ovarian reserve testing is a means to determine a woman’s fertility potential and provide an estimate of ovarian aging. Although chronological age alone serves as a useful marker of ovarian reserve, some women will experience a decline in their natural fertility sooner than expected, while some older women may maintain above average ovarian function. Identification of these two groups, with the ovarian reserve being inconsistent with chronological age, may be useful for counseling and planning treatment.
The most commonly used test of ovarian reserve is the cycle day three or basal Follicle Stimulating Hormone level. This is one of the essential reproductive hormones inhuman. An elevated basal FSH level is the first sign of ovarian aging that can is detected in women and usually occurs in women aged 35 to 40. Physiologically, the follicular pool reduces to approximately 10 per cent of the levels present at puberty. The rise in basal FSH is due to a loss in another set of reproductive hormones responsible for ovarian feedback called inhibin-A and B when the available follicular cohort diminishes.
Basal FSH levels are easy to obtain, and no special skills are required to perform the test or interpret the results; therefore, it is easily accessible. However, it is useful also to note that basal FSH levels have been shown to be predictive for inadequate response to ovarian stimulation and non-pregnancy only when the levels are extremely elevated. Elevated basal FSH levels are also less predictive of pregnancy for women at the age of 35.
An ovarian Antral Follicle Count is early in the menstrual cycle. Transvaginal ultrasound can identify the small circular fluid containing substances in the ovary called antral follicles between 2mm and 10 mm.
Antral follicles are sensitive to FSH and they are considered to be representative of the available follicle pool. The number of antral follicles seems to correlate with the number of primordial follicles in the ovary, with a decline in primordial follicles is reflected in a lower number of antral follicles.
The decrease in AFC may not be as steep as the decline in fertility, but the reduction in AFC correlates with both the menopause transition and ovarian response to stimulation.
The antimüllerian hormone (one of the reproductive hormones) produced by the granulosa cells of preantral and small antral follicles, but NOT dominant follicles. AMH levels decrease with decreasing AFC, which in turn is a marker of the possible eggs available at the early stage. Primordial follicle count levels remain consistent throughout the menstrual cycle and become undetectable in women after menopause. Although AMH provides moderate value in prediction of ovarian response in IVF, it is a poor predictor of pregnancy.
The clomiphene challenge test is performed by administering 100 mg of clomiphene daily from five to nine days of the cycle. FSH measured on day three and day 10. If an adequate response to clomiphene occurs, the rise in FSH is suppressed by the release of estradiol and inhibin-B by developing follicles. Systematic reviews have not shown a benefit to the clomiphene challenge test over basal FSH or AFC. Inhibin-B and basal estradiol have not been shown to be more useful predictors of inadequate response or pregnancy than basal FSH. However, basal estradiol levels are often screened in conjunction with FSH and they can confirm the correct timing in the menstrual cycle. An elevated estradiol level may also falsely suppress FSH levels.
In summary, as a rule of thumb, the fertility potential of a woman can be determined by the antral follicle count, the day three FSH.
Treatment of age-related infertility
Fertility treatment for age-related infertility is aimed at increasing monthly fecundity and decreasing the time to conception. Women may be offered Controlled ovarian hyper-stimulation with clomiphene citrate or gonadotropins, or In vitro fertilisation to improve their chances of pregnancy and reduce time to pregnancy.
Both treatments are intended to increase the number of mature oocytes each month to balance decreasing oocyte quality, but they do not address the underlying issue of oocyte quantity or quality although adjuvants, such as CoQ10, DHEA, Glutathione and other lifestyle modifications typified by the Modern Mayr Medicine type of detoxification, can be used to optimise the quality of the oocytes.
The only effective treatment for age-related infertility and declining oocyte quality is oocyte donation.
In reality, pregnancy and live birth rates with COH in older women are low. Older women may consider 1 to 2 cycles of COH if they do not want to try IVF as a first-line treatment, but they should move on to IVF quickly if they are unsuccessful within the first couple of cycles.
Although the chance of success diminishes with age, IVF still offers higher pregnancy and live birth rates than COH, although significantly lower rates than oocyte donation. Oocyte donation provides women with an intact uterus the opportunity to carry a pregnancy despite declining ovarian function or menopause.
Pregnancy rates with oocyte donation are based on the age of the donor, not on the age of the recipient. The truth is globally this has become an accepted procedure equally endorsed by the World Health Organisation to help those who may require it.
- Because of the decline in fertility and the increased time to the conception that occurs after the age of 35, women that are within this age bracket should get referred for infertility workup after six months of trying to conceive.
- Women in their 20s and 30s should be counseled about the age-related risk of infertility when other reproductive health issues, such as sexual health or contraception, are addressed as part of their primary well-woman care. Such women should be encouraged to seek fertility interventions on time. A delay will further reduce their chances of getting pregnant.
Reproductive-age women should be aware that natural fertility and assisted reproductive technology success is significantly lower for women in their late 30s and 40s.
- Ovarian reserve testing considered for women aged 35 years with risk factors for decreased ovarian reserve, such as a single ovary, previous ovarian surgery, and inadequate response to follicle – stimulating hormone, prior exposure to chemotherapy or radiation, or unexplained infertility
- Ovarian reserve testing before assisted reproductive technology treatment may be used for counseling but has a poor predictive value for non-pregnancy and should be used to exclude women from treatment only if levels are significantly abnormal.
- Pregnancy rates for controlled ovarian hyper-stimulation are low for women aged 40 years. Such women should consider IVF, if they do not conceive within 1 to two cycles of controlled ovarian hyper-stimulation.
- The only effective treatment for ovarian aging is oocyte donation. A woman with decreased ovarian reserve should be offered oocyte donation as an option, as pregnancy rates associated with this treatment are significantly higher than those related to controlled ovarian hyper-stimulation or in vitro fertilisation with a woman’s eggs.
In general, once the decision has been reached to have conception at an old age, it is essential to prepare the body like making the house while expecting a distinguished guest, and enter into a lifestyle cleansing protocol. It is the new stipulation for most cases of infertility. Studies have confirmed that some of the environmental toxins and nutritional allergies might have the adverse effect of conception.