Premature ovarian insufficiency (POI), is cessation of ovarian function characterized by
hypergonadotropic amenorrhea and hypoestrogenic syndrome before 40 years of age. About 1% of
women younger than 40 years old and 0.1% before 30 are affected. POI imposes a great
challenge on women's reproductive and long-term health, such as infertility, amenorrhea,
osteoporosis, and cardiovascular disease. Most patients already had impaired or complete loss
of fecundity when diagnosed. Currently, no optimal regimen exists to ameliorate ovarian
function. Typically, they end up with egg donation or adoption as an alternative way. Less
severe form of POI is diminished ovarian reserve (DOR). Although lack of consensus according
to Bologna criteria cut off for DOR was defined as (antral follicle count (AFC) <5-7
follicles or anti-Mullerian hormone (AMH) <0.5-1.1 ng/ml).
Previously it has been showed that 24% of women with POI had resumption of ovarian function
and 4% resulted in baby births. These data indicates residual follicles are available in
atrophic ovaries and have potential for development and even fertilization. In routine IVF
practice 15% percent of patients have poor ovarian response to ovarian stimulation. Patients
with DOR with a previous poor ovarian response (cycles cancelled or yielding ≤3 oocytes with
a conventional protocol) might have benefit from the strategies increasing follicle
activation and number of growing follicles and oocyte retrieved. Therefore, strategies
enabling ovarian resumption predictable and follicle activation feasible are promising for
POI/DOR treatment. Recently, In vitro Activation (IVA) approach has been proposed and live
births have been achieved in patients with POI. Phosphatase and tensin homolog (PTEN) enzyme
inhibitors and phosphatidylinositol-3 kinase activators could activate AKT pathway and
activate the dormant follicles. Ovarian fragmentation could lead to ovarian primary follicle
growth by interfering with Hippo signaling pathway. Residual follicles in patients with POI
could be activated to develop for egg retrieval by combination of mechanical and chemical
stimulation.
In 2019, Zhang et al retrospectively analyzed the follicle development and pregnancy outcome
in 80 POI patients after laparoscopic ovarian biopsy/scratch without using chemical agents as
was the case in IVA. 11 (13.75%) patients presented with ovarian function resumption, three
metaphases II oocytes were retrieved in 10 patients and two embryos were formed and freshly
transferred followed by a healthy singleton delivery in 1 (1.25%) patient. They concluded
that the technique of ovarian biopsy/scratch without chemical activation could promote
follicle development in vivo, suggesting it could bring promising benefits for some women
with POI.
In patient with POI/DOR, activation of residual follicles is a promising option and further
studies are warranted. Previous studies included laparoscopic surgery which may lead to
possible surgical complications. Without using chemical agents and laparoscopic surgery, main
object of this study is mechanical follicle activation with trans-vaginal ovarian needle
puncture with 17 gauge oocyte pickup needle in IVF patients with DOR.