Ovarian Rejuvenation

Ovarian rejuvenation is the umbrella term for experimental treatments that aim to reactivate dormant follicles in the ovarian tissue of women with diminished ovarian reserve or whose ovarian function has ceased at an early age. For this purpose, platelet-rich plasma (PRP) obtained from the patient's own blood is injected into the ovary. Exosome and stem cell applications are also described in the literature, although their safety and efficacy have not yet been scientifically established.

These methods are regarded as treatments whose efficacy has not yet been proven by large, controlled studies; they should therefore be considered not as a routine treatment option but as an experimental approach for selected patients, with informed consent.

Women are born with a limited number of egg cells, and this number declines irreversibly with age; after the age of 35 in particular, both the number and the quality of eggs fall markedly. Beyond this natural age-related process, risk factors that may contribute to an early decline in ovarian reserve include a family history of early menopause, genetic causes such as Turner syndrome and the fragile X premutation, autoimmune diseases, ovarian surgery (particularly endometrioma surgery), chemotherapy and radiotherapy, and smoking. Cessation of ovarian function before the age of 40 is called primary ovarian insufficiency and affects around 1% of women; in a significant proportion of patients no underlying cause is found.

Diminished ovarian reserve usually causes no symptoms and is detected during investigations for difficulty conceiving. Where symptoms are present, they may include shorter or longer cycles, irregular periods, lighter menstrual bleeding, a poor response to medication during IVF and a low number of eggs retrieved. In primary ovarian insufficiency, infrequent or absent periods may be accompanied by menopause-like symptoms such as hot flushes, night sweats, sleep disturbance, vaginal dryness and mood changes.

Ovarian reserve is mainly assessed by counting the small follicles in the ovaries, known as antral follicles, with a transvaginal ultrasound scan in the first days of the cycle, and by measuring the blood level of anti-Müllerian hormone (AMH). FSH and oestradiol levels measured on days 2–4 of the cycle also contribute to the diagnosis. An AMH level below 1.1 ng/mL and an antral follicle count below 5–7 are among the findings that suggest diminished reserve. Primary ovarian insufficiency is diagnosed when a woman under 40 has had no periods for at least 4 months and her FSH level, measured twice at least 4 weeks apart, is above 25 IU/L; genetic and autoimmune tests are recommended to investigate the underlying cause.

There is no proven treatment that fully reverses diminished ovarian reserve; treatment should be individualised according to the patient's age, the level of reserve and her wish to have children. For patients planning a pregnancy, IVF can be started without delay using stimulation protocols tailored to the individual.

In PRP, the most commonly used method, a blood sample taken from the patient is centrifuged in special tubes to separate the platelet-rich plasma, which is then injected into the ovary with a fine needle under brief sedation and transvaginal ultrasound guidance. The procedure takes around 15–30 minutes and, like egg collection, is carried out as a day case. The growth factors released by platelets are thought to act by increasing blood flow in the ovarian tissue and stimulating follicle development. Because a follicle takes around 3 months to develop from the dormant stage to ovulation, the effect of the procedure is usually assessed 1–3 months later by AMH, antral follicle count and cycle regularity.

Ovarian rejuvenation may be considered for women diagnosed with primary ovarian insufficiency, patients with a repeatedly poor ovarian response during IVF, and women in the transition to menopause (perimenopause) who wish to conceive. In these patients, the ovarian tissue must be visible on ultrasound before the procedure.

Because PRP is prepared from the patient's own blood, it carries no risk of allergic reaction or disease transmission and is generally considered safe. Rare procedure-related risks include pain at the injection site, light vaginal bleeding, intra-abdominal bleeding, infection and the risks associated with sedation.

In the studies published to date — mostly small, uncontrolled and reported as case series — some patients have shown increases in AMH and antral follicle count, a return of periods, more eggs and embryos obtained during IVF, and pregnancies achieved either naturally or through IVF after PRP. However, these results are not seen in every patient, the effect may be limited and temporary, and large controlled studies have not yet shown that it increases live birth rates. Ovarian rejuvenation should therefore be planned individually for each patient, with realistic expectations.