Autologous stem cell ovarian transplantation to increase reproductive potential in patients who are poor responders

Autologous bone marrow stem cell transplant improves ovarian reserve biomarkers and reproductive outcomes, allowing spontaneous pregnancies in poor responders. Positive effects could be mediated by specific soluble growth factors in apheresis.

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Volume 110, Issue 3, Pages 496–505.e1

Authors:

Sonia Herraiz, Ph.D., Mónica Romeu, M.D., Anna Buigues, B.Sc., Susana Martínez, M.D., César Díaz-García, M.D., Inés Gómez-Seguí, M.D., José Martínez, M.D., Nuria Pellicer, M.D., Antonio Pellicer, M.D.

Abstract:

Objective

To evaluate effects of autologous stem cell ovarian transplant (ASCOT) on ovarian reserve and IVF outcomes of women who are poor responders with very poor prognosis.

Design

Prospective observational pilot study.

Setting

University hospital.

Patient(s)

Seventeen women who are poor responders.

Intervention(s)

Ovarian infusion of bone marrow-derived stem cells.

Main Outcome Measure(s)

Serum antimüllerian hormone levels and antral follicular count (AFC), punctured follicles, and oocytes retrieved after stimulation (controlled ovarian stimulation) were measred. Apheresis was analyzed for growth factor concentrations.

Result(s)

The ASCOT resulted in a significant improvement in AFC 2 weeks after treatment. With an increase in AFC of three or more follicles and/or two consecutive increases in antimüllerian hormone levels as success criteria, ovarian function improved in 81.3% of women. These positive effects were associated with the presence of fibroblast growth factor-2 and thrombospondin. During controlled ovarian stimulation, ASCOT increased the number of stimulable antral follicles and oocytes, but the embryo euploidy rate was low (16.1%). Five pregnancies were achieved: two after ET, three by natural conception.

Conclusion(s)

Our results suggest that ASCOT optimized the mobilization and growth of existing follicles, possibly related to fibroblast growth factor-2 and thrombospondin-1 within apheresis. The ASCOT improved follicle and oocyte quantity enabling pregnancy in women who are poor responders previously limited to oocyte donation.

Clinical Trial Registration Number

NCT02240342.


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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

1 Comments

Go to the profile of Aniruddha Malpani
Aniruddha Malpani over 1 year ago

I would like to comment on this article by Herraiz and colleagues.


In this prospective observation pilot study of 17 women defined as PRs using the ESHRE criteria, bone marrow derived stem cells (BMDSC) were delivered directly to one ovary for each patient,  in an effort to optimize the recruitment of existing dormant follicles to improve IVF outcomes.


This was an interesting study design, because they had a built-in control. It was based on the hypothesis that infusing autologous stem cells into one ovary would selectively improve the ovarian response in that ovary, and this would presumably allow for the retrieval of more eggs from that when doing IVF, as compared to the contralateral ovary.  


This made a lot of intuitive sense, given all the hype surrounding stem cells in regenerative medicine, but sadly, this beautiful hypothesis was slayed by ugly facts. In fact, their own results showed that this infusion had no the number of punctured follicles in that ovary.  Sadly, they failed to share the number of eggs retrieved from the "treated" ovary versus the "control " ovary. However, their own results show that there was no difference in the AFC in the treated and control ovaries !


 It's interesting, but the dose of FSH required after ASCOT was more than the dose used prior to ASCOT , and the E2 level on Day of HCG administration was lower ( even though these results were not statistically significant, they are definitely not one would expect if their hypothesis was true).


The biggest tragedy is that instead of accepting that intraovarian autologous stem cell infusion does not affect ovarian response, they went ahead and massaged their data, to come up with a completely erroneous conclusion!


After subjecting patients to all that additional expense, they managed to achieve only 1 live birth in the post ASCOT IVF treatment cycle - hardly an impressive result, and one which could be purely because of chance !


They claim that this stem cell infusion improves pregnancy rates and ovarian response, but the reality is that most of the pregnancies which were achieved in the treatment group were natural pregnancies, and were treatment-independent  ! They conveniently confuse correlation with causation, and use the "post hoc, ergo propter hoc" illogic to justify this procedure.


The tragedy is that patients with poor PR are emotionally very vulnerable, and many doctors will now be tempted to use "advanced" techniques , which seem scientifically respectable, but have not been proven.


(1) Herraiz, S., Romeu, M., Buigues, A., Martínez, S., Díaz-García, C., Gómez-Sequí, I. et al. Autologous stem cell ovarian transplantation to increase reproductive potential in poor responder patients. Fertil Steril. 2018; 110: 173–182.e1