Autologous Platelet-rich Plasma (PRP) Infusion to Improve Outcomes in Women With Ovarian Insufficiency: a Pilot Study

Autologous Platelet-rich Plasma (PRP) Infusion to Improve Outcomes in Women With Ovarian Insufficiency: a Pilot Study

Autologous Platelet-rich Plasma (PRP) Infusion to Improve Outcomes in Women With Ovarian Insufficiency: a Pilot Study

The investigators propose a pilot study to determine if autologous platelet-rich plasma (PRP) improves ovarian reserves and In-vitro fertilisation (IVF) outcomes in women with diminished ovarian reserve / premature ovarian insufficiency.

Ovarian aging is a principal limiting factor for success in both spontaneous and assisted reproductive techniques (ART) conceptions. This results in diminished ovarian reserve (DOR) and premature ovarian insufficiency (POI), accounting for ~10% of IVF patients in Singapore and worldwide. Existing solutions include nutritional supplementations, high dose gonadotrophin usage, and experimental in-vitro activation with limited effectiveness, while donor oocyte programs or adoption do not provide a genetically related offspring. The substantial clinical burden and lack of effective treatments underscore the highly unmet need in this group of women. Intraovarian autologous platelet-rich plasma (PRP) infusion was recently introduced in the context of addressing ovarian insufficiency, with several studies showing an increase in ovarian function and promising ART outcomes. Possible mechanism includes anti-inflammatory and mitogenic potentials in this growth factor rich fraction contributing towards tissues regeneration. Through being involved in the cell regeneration cycle, autologous PRP potentially gives women with POI/DOR a hope in achieving a healthy genetically related offspring. It however, still remains an experimental technique as there are very few small studies published till date, with no locally published data on its use. The investigators propose a pilot study in KK Women's and Children's Hospital IVF (KKIVF) Centre to establish technical expertise, and to evaluate response to PRP to power a randomized controlled trial eventually. Primary outcomes are Anti-Mullerian Hormone (AMH), D2/3 Antral Follicle Count (AFC) and number of oocytes collected at stimulation. The secondary outcome will be clinical pregnancy and live birth rates. Thirty women with DOR/POI will be recruited over a 1 year period. The investigators hypothesize that PRP increases the overall pregnancy and live birth rates in these women.

Diminished Ovarian Reserve, Premature Ovarian Insufficiency, Poor Ovarian Reserve, Platelet-rich plasma, PRP, In Vitro Fertilisation (IVF), Fertility

All patients recruited will come down to KKIVF Centre on Day 2-3 of the menstrual cycle to do blood tests (Anti-Mullerian Hormone (AMH)) and an ultrasound scan (Antral Follicular Count (AFC)). In the same menstrual cycle/month, autologous PRP injection will be done on Day 5-15 of the cycle. Patients will return to KKIVF Centre 1-3 months after the PRP injection on Day 2-3 of the menstrual cycle to repeat blood tests (AMH) and Ultrasound scan (AFC). IVF stimulation cycle as per KKIVF protocol will be started within 6 months from PRP injection. Patients will be followed up as per routine, with no more additional visits pertaining specifically to the study.

PRP contains a high concentration of platelets which contains multiple vaso-active peptides and cytokines such as Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factor (PDGF) and Sphingosine-1-phosphate. Many of these cytokines have been implicated in important roles in ovarian function, follicular genesis and oocyte maturation. Intraovarian autologous PRP infusion was recently introduced in the context of addressing ovarian insufficiency, with several studies showing an increase in ovarian function and promising ART outcomes. Possible mechanisms include anti-inflammatory and mitogenic potentials in this growth factor rich fraction contributing towards tissues regeneration. Through being involved in the cell regeneration cycle, autologous PRP potentially gives women with premature ovarian insufficiency (POI) or diminished ovarian insufficiency (DOR) hope in achieving a healthy genetically related offspring.

Markers of ovarian reserve will be measured - Anti-Mullerian Hormone (AMH) levels on Day 2-3 of menses. Changes in ovarian reserve will be measured before and after the PRP infusion.

Markers of ovarian reserve will be measured - Antral Follicular Count (AFC) on Day 2-3 of menses. Changes in ovarian reserve will be measured before and after the PRP infusion.

This is defined as the presence of fetal heartbeat or gestational sac at 6-9 weeks after fresh embryo transfer.

Inclusion criteria Diminished ovarian reserves AND/OR; Anti-Mullerian Hormone (AMH) 0.2-0.5ng/ml or At least 2 Follicle Stimulating Hormone (FSH) readings of >25 (mIU/L) or AFC < 5 Poor Ovarian Response of <4 oocytes retrieved at a prior IVF stimulation cycle with gonadotrophin doses of 450u per day Exclusion criteria Amenorrhea of > 1 years Medical conditions - Diabetes Mellitus, Hypertension, Collagen vascular diseases, Thyroid disease Patients presenting with anemia and thrombophilic disorders Inability to be monitored for at least 1 year at the treating centre Lack of suitable sperm for Intracytoplasmic Sperm Injection (ICSI) (eg. Azoospermia)