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| courtesy: www.ivf-worldwide.com |
Premature
ovarian insufficiency (POI) affects 1 in 100 women below the age of 40 years. It causes amenorrhea, elevated FSH and hypoestrogenism.
Diagnosed with POI is a life changing situation for many women, especially
those who have still not completed their family. [1]
POI is due to early exhaustion of ovarian follicles due to genetic, autoimmune,
iatrogenic or other causes.[2]
Autologous ovarian
transplantation is used in patients with malignancy to preserve fertility while
radiotherapy and chemotherapy treatments. But, traditional transplantation is
not useful in patients with POI because the endocrine and reproductive functions
of the ovaries have already ceased. Until now, women with POI does conceive by In-Vitro
fertilization by donor’s egg or go for surrogacy or adoption. By undergoing
IVA, she has a chance to have her own biological child.
IVA or In
Vitro Activation, is a new procedure to obtain mature eggs for women with POI,
it involves a twostep procedure consisting of in vitro activation
of follicles followed by fragmentation into smaller ovarian cubes and
incubation with drugs before grafting. The second step consists of oocyte retrieval
followed by IVF and embryo transfer before pregnancy.
Phosphatase
and tensin homolog (PTEN) enzyme inhibitors and phosphatidylinositol-3 kinase
activators were used to activate the AKT pathway in dormant follicles leading to
follicular growth. Ovarian fragmentation also interferes with the Hippo signaling
leading to ovarian follicular development.[3]
A study
results published in The Journal of clinical endocrinology and metabolism have
translated this lab based IVA results into actual clinical practice resulting in
birth of two healthy babies without cryopreservation of the ovarian tissue.
In this groundbreaking
prospective observational cohort study, 14 patients with POI underwent IVA. The
women were average 4 years past LMP, around 29 years of age and mean FSH level of
94.5 mIU/mL.
All the patients
have received prior gonadotrophins treatment with no results before entering
the study. The larger of the two ovaries was removed by laparoscopy, cut into
strips and the strips were further cubed. The ovarian cubes were incubated to
activate the AKT pathway. The cubes were cultured for two days and after 2 days
of In Vitro activation they were transplanted back beneath the serosa of both
fallopian tubes. A part of the ovarian tissue was cryopreserved for use at
later date and 10-20% of the tissue was examined microscopically for residual
follicles.
The patients
underwent routine follicle stimulating protocols. Six (43%) of the fourteen patients
showed follicular development. Four patients had successful oocyte retrieval,
resulting in four embryos. Two women successfully delivered healthy infants
following embryo transfer while 3 embryos were cryopreserved for future use.
An earlier
study by Suzuki N et al published in Journal of Human Reproduction also reported
two successful live birth following
ovarian tissue vitrification in patients with primary ovarian insufficiency.[4]
"Although
I believed, based on our previous research, that this IVA approach would work,
I monitored the pregnancy closely and, when the baby was in a breech
presentation, I performed the caesarean section myself," said Dr. Kazuhiro
Kawamura, an associate professor of obstetrics and gynecology who led the team
at St. Marianna.
"I
could not sleep the night before the operation, but when I saw the healthy
baby, my anxiety turned to delight. The couple and I hugged each other in
tears. I hope that IVA will be able to help patients with primary ovarian
insufficiency throughout the world."
Future
randomized studies are needed before IVA can become a part of routine clinical
practice for infertility patients. The researchers are considering several
aspects like new drugs to target the Hippo and PTEN pathways to stimulate the
ovaries without surgery.
It is too early
to say that it can be used for wider application, but a new option has
certainly been added to the ART armamentarium.
[1] http://www.uptodate.com/contents/early-menopause-primary-ovarian-insufficiency-beyond-the-basics
[2] http://humrep.oxfordjournals.org/content/early/2015/01/06/humrep.deu353.full.pdf
[3] Kawamura
K, Cheng Y, Suzukia N, et al. Hippo signaling disruption and Akt stimulation of
ovarian follicles for infertility treatment.
PNAS. 2013.
[4] Suzuki
N, Yoshioka N, Takae S, Sugishita Y, Tamura M, Hashimoto S, Morimoto Y,
Kawamura K.
Hum Reprod. 2015 Mar;30(3):608-15
