Usefulness of individualized FSH, LH and GH dosing in ovarian stimulation of women with low ovarian reserve

Usefulness of individualized FSH, LH and GH dosing in ovarian stimulation of women with low... Sir, We read with interest the multicentre prospective study by van Tilborg et al. (2017) concluding that individualized FSH dosing, based on antral follicle count (AFC), does not improve live-birth rates or reduce costs as compared to a standard FSH dose. This is likely to be true for women with predicted normal response to controlled ovarian hyperstimulation (COH). As to hyper-responders, individualized FSH dosing appeared to reduce the risk of mild and moderate ovarian hyperstimulation syndrome (OHSS). On the other hand, the conclusions related to low and extremely low responders are not clear. First of all, values of anti-Müllerian hormone (AMH) were included only retrospectively and were not taken into account in the decision about patients’ eligibility. Yet, AMH, together with AFC, is an important predictor of poor ovarian reserve (Ferraretti et al., 2011). Moreover, the lower limit of AFC for patient inclusion is not mentioned, and the authors admit that AFC evaluation may have been subject to inter-observer variability (van Tilborg et al., 2017). It is thus important to make clear that their conclusions cannot be applied to women with poor and extremely poor ovarian reserve. According to Kedem et al. (2013), poor and extremely poor ovarian reserve is characterized by serum AMH values of ≤1.1 ng/ml and ≤0.2 ng/ml, respectively. In a recent study, we have reported unexpectedly high-clinical pregnancy and delivery rates achieved in a group of 78 women with extremely poor ovarian reserve by using a patient-tailored protocol of FSH, LH and growth hormone (GH) dosing for ovarian stimulation (Tesarik, 2017). Some of these women were starting their first IVF or ICSI treatment, similar to the group evaluated in the paper by van Tilborg et al. (2017), but all of them had been refused to be treated by other clinics because of their extremely low (≤0.2 ng/ml) serum AMH levels. Some of these women had no antral follicles detectable by ultrasound before the beginning of ovarian stimulation. Because of the rapid decline of their ovarian reserve, there was no time for planning a randomized control trial for these women. There is thus no evidence of how they would respond to a standard ovarian stimulation protocol. However, our previously published observations show that individualized dosing of FSH, LH and GH can be of help in ovarian stimulation in different clinical conditions (Tesarik and Mendoza, 2002, Tesarik et al., 2005). The difference between an individualized protocol and a standard one may be marginal in women with normal ovarian reserve. However, in women with poor or extremely poor ovarian reserve, customization of COH protocols appears to be important. In conclusion, we agree that individualized COH protocols may be unsuccessful, or even disadvantageous from the cost-effectiveness point of view, in a majority of women starting their first IVF/ICSI attempt, most of which are likely to be normo-responders. However, it would be wrong to generalize this conclusion because individualized protocols may be advantageous for certain categories of women, namely for those with a poor or extremely poor ovarian reserve. Conflict of interest The authors have no conflicts of interest to declare. References Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L. ESHRE consensus on the definition of ‘poor response’ to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod  2011; 26: 1616– 1624. Google Scholar CrossRef Search ADS PubMed  Kedem A, Haas J, Geva LL, Yerushalmi G, Gilboa Y, Kanety H, Hanochi M, Maman E, Hourvitz A. Ongoing pregnancy rates in women with low and extremely low AMH levels. A multivariate analysis of 769 cycles. PLoS One  2013; 8: e81629. Google Scholar CrossRef Search ADS PubMed  Tesarik J. Customized assisted reproduction enhancement (CARE) for women with extremely poor ovarian reserve (EPOR). J Gynecol Women’s Health  2017; 3. DOI: 10.19080/JGWH.2017.03.555625. Tesarik J, Hazout A, Mendoza C. Improvement of delivery and live birth rates after ICSI in women ageg 40 years by ovarian co-stimulation with growth hormone. Hum Reprod  2005; 20: 2536– 2541. Google Scholar CrossRef Search ADS PubMed  Tesarik J, Mendoza C. Effects of exogenous LH administration during ovarian stimulation of pituitary down-regulated young oocyte donors on oocyte yield and developmental competence. Hum Reprod  2002; 17: 3129– 3137. Google Scholar CrossRef Search ADS PubMed  van Tilborg TC, Oudshoorn SC, Eijkemans MJC, Mochtar MH, van Golde RJT, Hoek A, Kuchenbecker WKH, Fleischer K, de Bruin JP, Groen H et al.  . Individualized FSH dosing based on ovarian reserve testing in women starting IVF/ICSI:a multicentre trial and cost-effectiveness analysis. Hum Reprod  2017; 32: 2485– 2495. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Human Reproduction Oxford University Press

Usefulness of individualized FSH, LH and GH dosing in ovarian stimulation of women with low ovarian reserve

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Abstract

Sir, We read with interest the multicentre prospective study by van Tilborg et al. (2017) concluding that individualized FSH dosing, based on antral follicle count (AFC), does not improve live-birth rates or reduce costs as compared to a standard FSH dose. This is likely to be true for women with predicted normal response to controlled ovarian hyperstimulation (COH). As to hyper-responders, individualized FSH dosing appeared to reduce the risk of mild and moderate ovarian hyperstimulation syndrome (OHSS). On the other hand, the conclusions related to low and extremely low responders are not clear. First of all, values of anti-Müllerian hormone (AMH) were included only retrospectively and were not taken into account in the decision about patients’ eligibility. Yet, AMH, together with AFC, is an important predictor of poor ovarian reserve (Ferraretti et al., 2011). Moreover, the lower limit of AFC for patient inclusion is not mentioned, and the authors admit that AFC evaluation may have been subject to inter-observer variability (van Tilborg et al., 2017). It is thus important to make clear that their conclusions cannot be applied to women with poor and extremely poor ovarian reserve. According to Kedem et al. (2013), poor and extremely poor ovarian reserve is characterized by serum AMH values of ≤1.1 ng/ml and ≤0.2 ng/ml, respectively. In a recent study, we have reported unexpectedly high-clinical pregnancy and delivery rates achieved in a group of 78 women with extremely poor ovarian reserve by using a patient-tailored protocol of FSH, LH and growth hormone (GH) dosing for ovarian stimulation (Tesarik, 2017). Some of these women were starting their first IVF or ICSI treatment, similar to the group evaluated in the paper by van Tilborg et al. (2017), but all of them had been refused to be treated by other clinics because of their extremely low (≤0.2 ng/ml) serum AMH levels. Some of these women had no antral follicles detectable by ultrasound before the beginning of ovarian stimulation. Because of the rapid decline of their ovarian reserve, there was no time for planning a randomized control trial for these women. There is thus no evidence of how they would respond to a standard ovarian stimulation protocol. However, our previously published observations show that individualized dosing of FSH, LH and GH can be of help in ovarian stimulation in different clinical conditions (Tesarik and Mendoza, 2002, Tesarik et al., 2005). The difference between an individualized protocol and a standard one may be marginal in women with normal ovarian reserve. However, in women with poor or extremely poor ovarian reserve, customization of COH protocols appears to be important. In conclusion, we agree that individualized COH protocols may be unsuccessful, or even disadvantageous from the cost-effectiveness point of view, in a majority of women starting their first IVF/ICSI attempt, most of which are likely to be normo-responders. However, it would be wrong to generalize this conclusion because individualized protocols may be advantageous for certain categories of women, namely for those with a poor or extremely poor ovarian reserve. Conflict of interest The authors have no conflicts of interest to declare. References Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L. ESHRE consensus on the definition of ‘poor response’ to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod  2011; 26: 1616– 1624. Google Scholar CrossRef Search ADS PubMed  Kedem A, Haas J, Geva LL, Yerushalmi G, Gilboa Y, Kanety H, Hanochi M, Maman E, Hourvitz A. Ongoing pregnancy rates in women with low and extremely low AMH levels. A multivariate analysis of 769 cycles. PLoS One  2013; 8: e81629. Google Scholar CrossRef Search ADS PubMed  Tesarik J. Customized assisted reproduction enhancement (CARE) for women with extremely poor ovarian reserve (EPOR). J Gynecol Women’s Health  2017; 3. DOI: 10.19080/JGWH.2017.03.555625. Tesarik J, Hazout A, Mendoza C. Improvement of delivery and live birth rates after ICSI in women ageg 40 years by ovarian co-stimulation with growth hormone. Hum Reprod  2005; 20: 2536– 2541. Google Scholar CrossRef Search ADS PubMed  Tesarik J, Mendoza C. Effects of exogenous LH administration during ovarian stimulation of pituitary down-regulated young oocyte donors on oocyte yield and developmental competence. Hum Reprod  2002; 17: 3129– 3137. Google Scholar CrossRef Search ADS PubMed  van Tilborg TC, Oudshoorn SC, Eijkemans MJC, Mochtar MH, van Golde RJT, Hoek A, Kuchenbecker WKH, Fleischer K, de Bruin JP, Groen H et al.  . Individualized FSH dosing based on ovarian reserve testing in women starting IVF/ICSI:a multicentre trial and cost-effectiveness analysis. Hum Reprod  2017; 32: 2485– 2495. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

Human ReproductionOxford University Press

Published: May 1, 2018

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