Modified natural cycle IVF for poor responders

Jerome H. Check

Professor Obstetrics and Gynecology, Division Head of Reproductive Endocrinology & Infertility,Robert Wood Johnson Medical School at Camden,7447 Old York Road, Melrose Park, PA 19027, USA

Email: laurie{at}ccivf.com

Sir,

The article by Kolibianakis et al. (2004)Go has concluded that the retrieval of an oocyte(s) in women with high day 3 FSH and poor ovarian reserve using a modified natural cycle protocol is not an effective treatment. They state that ‘patients should be counselled appropriately and either proceed to oocyte donation or abandon infertility treatment’. I write this letter to vehemently disagree with this last statement (Kolibianakis et al., 2004Go).

Their manuscript was submitted March 15, 2004 and resubmitted May 11, 2004, so unfortunately they did not have access to an article we recently published concerning 259 retrieval cycles and 72 transfers in poor responders using minimal or no gonadotrophin stimulation without agonists or antagonists (Check et al., 2004Go). These patients were divided into four age groups (≤35, 36–39, 40–42 and ≥43 years) and their mean serum day 3 FSH levels were 19.7, 20.6, 18.8 and 21.9 mIU/ml. If one eliminates the oldest group, the delivered pregnancy rate for 47 embryo transfers in women up to 42 years of age was 12/47 (25.5%). Approximately 50% of retrievals resulted in an embryo (about half were transferred fresh and half frozen). The median number of embryos transferred was one. The implantation rate was 21.6% (13/60) for the three groups and was 33.3% for patients aged ≤35 years and 28.6% for women aged 36–39 years (Check et al., 2004Go). We have in fact published a case report of a 42 year old woman with tubal factor in imminent menopause who did not progress past the early antral stage either naturally or with gonadotrophins who responded to restoration of down-regulated FSH receptors by lowering the elevated serum FSH with ethinyl estradiol alone without gonadotrophins and was able to form a mature follicle and delivered a live baby following transfer of a single embryo (Check et al., 2002Go). Another woman in imminent menopause who failed to attain a mature follicle on her own or with gonadotrophins alone was able to respond to gonadotrophins once her FSH was suppressed by ethinyl estradiol and she successfully delivered following transfer of two embryos (Check et al., 2000Go).

I tried to see if there are differences in methodology. We waited for the follicle to attain an 18 mm average diameter instead of 16 mm as performed by Kolibianakis et al. and we retrieved the oocyte at 34–36 h from hCG injection rather than 32 h. Admittedly we missed the oocyte about half the time (though retrieval was avoided). Also our protocol usually, but not always, lowered the serum FSH with ethinyl estradiol.

The authors do state that ‘the possibility cannot be excluded that modifications of the protocol applied in the current study could be associated with an improved outcome’. Despite this caveat, however, the authors concluded with the extremely strong negative statement previously quoted, suggesting donor oocytes or abandoning infertility treatment.

For many couples the use of donor oocytes is precluded for religious, personal, legal, or financial reasons. The majority of the patients that we treated were told that IVF could not work for them and that their only choice was donor oocyte or adoption. Though our data are published and available to physicians to read, Human Reproduction is one of the two frequently read infertility journals and the data by Kolibianakis et al. are likely to profoundly influence treating physicians. Even more worrisome, based on the gruesome statistics that they present, is that many insurance companies paying for IVF may use these data as reasons to exclude patients from this benefit when they have decreased oocyte reserve. I thank Human Reproduction for the opportunity to present to the readership somewhat more encouraging data and would welcome the opinions of Kolibianakis et al. about my concerns.

References

Check JH, Summers D, Nazari A and Choe J (2000) Successful pregnancy following in vitro fertilization-embryo transfer despite imminent ovarian failure. Clin Exp Obstet Gynecol 27, 97–99.[Medline]

Check ML, Check JH, Choe JK and Berger GS (2002) Successful pregnancy in a 42-year-old woman with imminent ovarian failure following ovulation induction with ethinyl estradiol without gonadotropins and in vitro fertilization. Clin Exp Obstet Gynecol 29, 11–14.[Medline]

Check ML, Check JH, Wilson C, Choe JK and Krotec J (2004) Outcome of in vitro fertilization-embryo transfer according to age in poor responders with elevated baseline serum follicle stimulation hormone using minimal or no gonadotropin stimulation. Clin Exp Obstet Gynecol 31, 183–184.[Medline]

Kolibianakis E, Zikopoulos K, Camus M, Tounaye H, Van Steirteghem A and Devroey P (2004) Modified natural cycle for IVF does not offer a realistic chance of parenthood in poor responders with high day 3 FSH levels, as a last resort prior to oocyte donation. Hum Reprod 19, 2545–2549.[Abstract/Free Full Text]

Submitted on January 19, 2005; accepted on April 5, 2005.





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