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• W2021329596 abstract "We read with interest the review “Evaluating strategies for improving ovarian response of the poor responder undergoing assisted reproductive techniques” by Surrey and colleagues (1Surrey E.S. Schoolcraft W.B. Evaluating strategies for improving ovarian response of the poor responder undergoing assisted reproductive techniques.Fertil Steril. 2000; 73: 667-676Abstract Full Text Full Text PDF PubMed Scopus (256) Google Scholar). We agree with the contents of the review and would like to make two points concerning the definition of poor responders and a possible role of GnRH antagonist improving the outcome of poor responders. It is confusing to have so many different definitions for poor responders. This makes comparison between different studies impossible, and, furthermore, what was considered a poor response in some of the studies might actually have been from a relatively low dose of gonadotropin, omitting an extra allowance for increased patient body weight or age. Moreover, lack of a consistent definition of poor response makes it difficult to develop or assess any protocol to improve the outcome. One of the authors published a definition for poor responders elsewhere, taking into consideration the above-mentioned variables (2Gorgy A. Naumann N. Bates S. Craft I.L. Assisted conception following poor ovarian response to gonadotrophin stimulation.[letter, comment] Br J Obste Gynaecol. 1997; 104: 1420-1421Crossref PubMed Scopus (4) Google Scholar). Poor responders can be divided into two groups. The young poor responders are patients who are ≤37 years old and weigh ≤70 kg whose cycles were abandoned because they developed fewer than five progressing follicles, as assessed by vaginal ultrasound scan, following 9 days of an average daily dose of 225 IU of gonadotropin injections; or those who proceeded to oocyte retrieval and required a total dose of more than 600 IU of gonadotropin per retrieved oocyte. An extra allowance of up to 75 IU of gonadotropin in the daily dose should be considered for overweight patients and those who are ≥38 years old. Poor response in patients who are ≥38 years old is fundamentally due to age, while overweight patients usually do better if they lose weight. The above-mentioned definition is supported by the results of Land et al., who restimulated their poor responders by doubling the dose of gonadotropins (450 vs. 225 IU) (3Land J.A. Yarmolinskaya M.I. Dumoulin J.C. Evers J.L. High dose human menopausal gonadotropin stimulation in poor responders does not improve in vitro fertilization outcome.Fertil Steril. 1996; 65: 961-965Abstract Full Text PDF PubMed Scopus (215) Google Scholar). Eighty-nine of 126 poor responders proceeded to oocyte retrieval with a mean number of 7.5 ± 4.5 oocytes on an average total number of 67.1 ± 6.7 ampules of human menopausal gonadotropin (HMG), i.e., 9 ampules (675 IU) of HMG per retrieved oocyte (still poor response according to our definition). The outcome was still poor, with a pregnancy rate of 3.2% per cycle (4.4% per ovum pickup). Although the level of naturally released GnRH in the human body is too low to affect the extrapituitary GnRH receptors, the level of the agonists given to achieve down-regulation might be high enough to interact with these receptors. GnRH agonists, particularly in high dose or depot form, might contribute to poor response in some patients. The presence of GnRH receptors in the ovaries has been recently confirmed by Leung (4Leung P.C.K. GnRH receptor and potential action in human ovary.Gynaecol Endocrinol. 1999; 13: 10Google Scholar). This view might also explain the improved response of poor responders when the GnRH agonist was discontinued or reduced after a week of administration and when a micro dose of GnRH agonist was given by the authors of the review (5Faber B. Mayer J. Cox B. Jones D. Toner J. Oehninger S. et al.Cessation of gonadotropin releasing hormone agonist therapy combined with high-dose gonadotropin stimulation yields favorable pregnancy results in low responders.Fertil Steril. 1998; 69: 826-830Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar). One of the authors considered the use of GnRH antagonist Cetrotide (cetrorelix; Asta Medica, Frankfurt, Germany) in a small daily dose (0.25 mg) to prevent premature LH surge in treating poor responders (including all age groups) (6Craft I. Gorgy A. Hill J. Menon D. Podsiadly B. Will GnRH antagonists provide new hope for patients considered “difficult responders” to GnRH agonist protocols?.Hum Reprod. 1999; 14: 2959-2962Crossref PubMed Scopus (122) Google Scholar). As the antagonist is introduced late in the ovarian stimulation phase (day 7 of the cycle after 5 days of stimulation or when the leading follicle reaches 14 mm in diameter), the period of exposure to the analogue is reduced. Lack of down-regulation early in the cycle allows the ovaries to respond maximally to administered gonadotropin in addition to the naturally released pituitary FSH and LH and eliminates any possible adverse effect of GnRH agonist during the early phase of stimulation. The initial experience with the GnRH antagonist cetrorelix protocol for poor responders in which the patients produced a higher number of oocytes on a relatively lower total dose of gonadotropin per retrieved oocyte was previously published (6Craft I. Gorgy A. Hill J. Menon D. Podsiadly B. Will GnRH antagonists provide new hope for patients considered “difficult responders” to GnRH agonist protocols?.Hum Reprod. 1999; 14: 2959-2962Crossref PubMed Scopus (122) Google Scholar). The pregnancy and live birth rates also improved. This has been recently confirmed by reviewing the cumulative data of 68 treatment cycles on GnRH antagonist protocol for 48 poor responders as compared with their previous 64 cycles on GnRH agonist protocol. Both pregnancy and live birth rates improved: 11.8% vs. 6.25% and 7.4% vs. 1.6%, respectively (unpublished data). Unfortunately, Surrey and his colleagues failed to quote the above-mentioned strategy, which might be the one of choice in the future. Poor response is one of the most frustrating problems in assisted reproduction. A standard definition is urgently needed, and properly designed studies are required to assess the proposed strategies to improve the outcome. September 4, 2000 The work on the cetrorelix protocol was performed during the author’s previous post at London Fertility Centre, London." @default.
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• W2021329596 title "Defining and predicting the poor responder!" @default.
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