Natural ovarian stimulation (NATOS): effectively natural


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Volume 107, Issue 5, Pages 1120–1121


Renato Fanchin, M.D, Ph.D.


Given that the so-called “mild” ovarian stimulation procedures, together with their underlying die-hard ideology are, finally, running out of steam under the blows of evidence-based medicine and patient choices, the time has come to take over the concept of “natural” in reproductive care—this time, in the name of efficacy. Indeed, numbers in France indicate the cost of live birth through in vitro fertilization (IVF)-embryo transfer (ET) exceeds US$15,000-, mainly because per-cycle effectiveness of treatments remains low in France and patients often need to undergo repeated cycles to finally conceive.

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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.


Go to the profile of Micah J Hill
almost 4 years ago
Dr Fanchin,
Thank you for this update on a very interesting study concept. I have two theoretical concerns based on the literature.
1. FSH only stimulation protocols have higher levels of premature progesterone rise. So do antagonist protocols. Additionally, antagonists have been demonstrated to suppress aromatase production. In the ganirelix dose finding study (HR 1998), doses of ganirelex over 1000 mcg profoundly suppressed LH. Since you are driving steroid production with FSH stimulation of StAR and SCC, but minimally stimulating CYP17 expression by suppressing LH levels and giving no exogenous LH, is there a concern that you might see a large build up of serum P in these patients? If you are stimulating the entry point of the pathway, but blocking it downstream, it seems that there must be a build up of some intermediate in the pathway as a result?
2. Also from the ganirelix dose finding study, pregnancy rates were 33% with the 250mcg dose, but dropped to 10%, 14%, and 0% at doses of 500mcg, 1000mcg, and 2000mcg respectively. Are you concerned that your 1500mcg dose, despite effectively suppresing estradiol, may also suppress pregnancy? If not, why do you think this prior RCT saw these low pregnancy rates at high ganirelix doses?
Thank you for your thoughts on these questions that came to my mind reading your editorial. I'm very curious how you thought about these issues as you designed this trial. And very interested to see what the results show.
Go to the profile of Lee Gyeong Hun
almost 4 years ago
Dr Fanchin.
really interested to read your interesting concept. I have some concerns on terms related to NATOS (natural ovarian stimulation).
this concepts contains high dose GnRHant and recFSH for IVF, aiming to suppress LH level. It looks similar to natural IVF in terms of hormonal profile during COH, but may give some confusion to us in terms that so many injections was used to lower LH level.
Natural-like ovarian stimulation (NaLOS), I guess, may be perferable to NATOS in order to avoid some confusion to the beginners including me.
I also really want ot see what the results show