According to the European Society of Human Reproduction and Embryology (ESHRE):

  • One in six couples worldwide experience some form of infertility problem at least once during their reproductive lifetime. The current prevalence of infertility lasting for at least 12 months is estimated to affect between 8-12% worldwide for women aged 20-44.
  • 20-30% of infertility cases are explained by physiological causes in men, 20-35% by physiological causes in women, and 25-40% of cases are because of a problem in both partners. In 10-20% no cause is found. Infertility is also associated with lifestyle factors such as smoking, body-weight and stress.
  • Increasing age in the female partner is one of the most common explanations today.
  • Most ART treatments take place in women aged between 30 and 39.

Ovarian Insufficiency

As defined by the World Health Organization, ovarian insufficiency can be caused by a primary disorder in the ovary or it can occur as a result of secondary causes. Ovarian insufficiency is considered primary if the ovary fails to function normally in response to appropriate gonadotropin stimulation provided by the hypothalamus and pituitary. Ovarian insufficiency is considered secondary if the hypothalamus and pituitary fail to provide appropriate gonadotropin stimulation. OI is further characterized by, for example, decreasing of Anti-Mullerian Hormone (AMH), increasing of Follicle-Stimulating Hormone (FSH), a decreased Antral Follicle Count (AFC) and a low oocyte quality compared to healthy female subjects. The oocytes produced by a female subject with OI are typically of poorer quality as compared to those produced by females with good ovarian reserve. OI includes Diminished Ovarian Reserve (DOR), Premature Ovarian Failure (POF), Primary Ovarian Insufficiency (POI) and Poor Ovarian Response (POR).

Current Treatments

Currently, the only method of achieving pregnancy in OI subjects is by means of Assisted Reproductive Techniques (ART), such as In Vitro Fertilisation (IVF), which requires ovarian stimulation with high doses of gonadotropins. Various modalities have been tried to improve the outcome in subjects with OI undergoing assisted reproductive technology. These include high-dose FSH treatment, Luteinising Hormone (LH) supplementation, Gonadotropin-Releasing Hormone (GnRH) antagonist cycle, and use of adjuvant treatments such as estradiol priming, growth hormone, L-arginine and Dehydroepiandrosterone (DHEA). These gonadotropin and fertility treatments have negative side effects such as abdominal pain, nausea, vomiting, weight gain, acne, breast pain or tenderness and mood swings, which can lead to discontinued treatment. Further, although gonadotropin treatments are widely used to promote the development of early antral follicles to the pre-ovulatory stage, many OI subjects do not respond to the gonadotropin therapy. Female subjects with OI may have fewer numbers of oocytes during oocyte retrieval; hence, fewer embryos for transfer and fewer chances of conception when compared with a female subject having normal ovarian reserve. These OI subjects may need cancellation of the IVF cycle midway either due to the absence of follicular development, due to lack of oocytes retrieved, lack of successful fertilization or increased pregnancy failure (e.g. high miscarriage rate, which is thought to be due to the initial low oocyte quality found in OI subjects). Generally, IVF is not very helpful for these subjects because as patient age increases, the rate of success decreases dramatically. Although the global success rate of IVF is 25%, which is very low, the success rate in patients between 38-39 years old is 20.8% and for the 40-42, 43-44, 45 and over age ranges it is 13.6%, 5% and 1.9% respectively. This leads many OI subjects to either rely on donor oocyte programs or adoption programs.