New Hope : Stem Cell Therapy In Infertility

Dr . Varsha Baste Nashik

DR. VARSHA BASTE PRACTISING GYNAECOLOGIST IN NASHIK SINCE 25

YEARS. DIRECTOR - PUSHPA FERTILITY CENTRE NASHIK, SINCE 15

YEARS. CEO Founder, Cell Gen Anti Aging Center.

First Adult Stem Cell Therapy Center in Western India. FIRST ICSI, PGD BABY IN NORTH MAHARASHTRA (2003). FOUNDER MEMBER ISAR – MAHARASHTRA CHAPTER. PRESTIGIOUS DR. ANANDIBAI JOSHI AWARDEE. FELICITATED BY TEJASHWINI AWARD, (FOR WOMAN OF

SUBSTANCE). CHAIRPERSON, PPIM WEST ZONE INFERTILITY

CONFERENCE, IFS( 2014). PAST PRESIDENT – OBGY SOCIETY, NASHIK.

Stem Cells as New Agents for The

Treatment of female Infertility

BACKGROUND

Nearly 72.4 million people or 15% of couples experience fertility problems. 1 in 6 reported couples.

Infertility is a heterogeneous condition, caused by various underlying pathologies, it is possible that some of the mechanisms leading to infertility.

Due to their unlimited source and high differentiation potential, stem cells are considered as potentially new therapeutic agents for the treatment or infertility.

Stem cell-derived male gametes. Several growth factors and cytokines are used for in vitro

Differentiation of pluripotent cells into male gametes/SSC-like cells.

The transplantation of Stem cell-derived SSC-like cells in sterile mice results in proper spermatogenesis

Stem cell-based strategies for ovarian regeneration and oocyte production have been proposed as future clinical therapies for treating infertility in women.

Ovarian stem cells:isolation and regenerative potential.

Ovarian stem cells (MVH+BrdU+ cells) residing within the ovarian surface epithelium of neonatal and adult mice express high telomerase activity, Oct4, and Nanog and have a capacity to generate functional oocytes when transplanted back into sterile recipient mice .

ENDOMETRIOSIS

MSCs are being tested as a new potential therapy for endometriosis. The overall aim of this research is to examine the effect of MSCs on the characteristics and functions of endometriotic epithelial cells(EECs) and endometriotic stromal cells(ESCs),as well as immune cells . MSCs could provide a new and potentially effective therapy for endometriosis.

Transplantation of MSCs may reduce the inflammation and there by alleviate the pain, and reduce the infertility seen in patients with endometriosis

Autologous stem cell transplantation in refractory

Ashermann's syndrome: A novel cell based therapy

There is substantial evidence that adult stem cell populations exist in human endometrium, and hence it is suggested that either endogenous endometrial stem/progenitor cells can be activated or bone marrow derived stem cells can be transplanted in the uterine cavity for endometrial regeneration in Asherman's syndromeSix cases of refractory AS with failed standard treatment option of hysteroscopic adhesiolysis in the past were included. Mononuclear stem cells (MNCs) were implanted in sub-endometrial zone followed by exogenous oral oestrogen therapy. Endometrial thickness (ET) was assessed at 3, 6, and 9 monthsMean of ET (mm) at 3 months (4.05 ± 1.40), 6 months (5.46 ± 1.36) and 9 months (5.48 ± 1.14) were significantly (P < 0.05) increased from pre-treatment level (1.38 ± 0.39). Five out of six patients resumed menstruation.The autologous stem cell implantation leads to endometrial regeneration reflected by restoration of menstruation in five out of six cases. Autologous stem cell implantation is a promising novel cell based therapy for refractory AS.

Response of autologous mononuclear stem cells +PRPinfusion to infertile female patients of thin

endometrium at CELL GEN center , Nashik .

Around 27 patients treated with intra uterine infusion of PRP +mononuclear cells .

• Patient selection on criteria :Previous history of thin endometrium and cycle cancellation.Repeated IVF failures . Repeated abortions.Elderly with thin endometrium Endometriosis or adenomyosis.

Patients received treatments for 1 to 2 times in same or twoconsecutive cycles .

Outcome -

Around 17 patients conceived with ongoing viable pregnancies.

Now our trend is to give such therapy to all high risk patients and resistantcases irrespective of endometrial status.

In my view ,if we inject SCTS in the basal layer or in myometrium through endometrial cavity will yield better result improving the vascularization and outcomes. Our trials are going on.

MSCS mainly useful for – Partial Ashermanns Syndrome

About 0.6 ml of MSCS / BMSC infused in the endometrial cavity 1 to 2 times to improve vascularization and to decrease adhesion and to get endometrial lining.

We have very less experience in this field.

Use of stem cells in production of gametes like oocytes and sperms is an ongoing intensive research .

The procedure for case of premature ovariun failure.

Ovarian small tissues are removed and invitro stimulation is done in lab by dipping them in stem cells and growth factors .

New oogonia start to develop.

These newly harvested ovarian small pieces again implanted under the patients broad ligament below her fallopian tubes laparoscopically.

The patient is then stimulated with gonadotrophins and IVF performed.

This is new breakthrough achieved for patients of premature ovarian insufficiency ,ovarian failure or menopausal elderly patients.

Role of Stem Cells in Infertility

Autologous platelet-rich plasma & Mono Nuclear Cells promotes endometrial growth and improves pregnancy outcome during in vitro fertilization

The effectiveness of PRP in the therapy of infertile women with thin endometrium (≤ 7 mm). Material and methods: Five women undergoing in vitro fertilization (IVF) with poor endometrial response still had thin endometrium (< 7 mm) after standard hormone replacement therapy (HRT) and had to cancel embryo transfer cycle. In addition to HRT, intrauterine infusion of PRP was performed. PRP was prepared from autologous blood by centrifugation, and 0.5-1 ml of PRP was infused into the uterine cavity on the 10th day of HRT cycle. If endometrial thickness failed to increase 72 h later, PRP infusion was done 1-2

Autologous Platelet-rich plasma promotes pregnancy

Treatment assessment Endometrial thickness was measured at the thickest part at the longitudinal axis of the uterus by an experienced ultrasonographer (Figure 1). The thickness was measured thrice to confirm thin endometrium, and the average from 3 measurements was recorded. The primary end- point was endometrial thickness measured in transvaginal sonography, the second endpoint was clinical pregnancy after embryo transfer. Clinical pregnancy was confirmed when an intrauterine gestational sac was identified by transvaginal ultrasonography and an increase in serum β-HCG was present.

Results The endometrial thickness increased at 48-72 h after PRP infusion in all the patients, and reached > 7 mm on the day of progesterone administration. Patients 1, 2 and 5 underwent transfer of two blastocysts, patient 3 had transferred one blastocyst and patient 4 had transferred two cleavage-stage embryos. Cleavage- stage embryos were transferred on the 3rd day after progesterone administration, and blastocysts

CONCLUSION

Stem cells play an important role in the management of female infertility and with the help of this regenerative medicine has much scope in the treatment of Infertility to achieve promising results in near future !!