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Live birth rates after modified natural cycle compared with high-dose FSH stimulation using GnRH antagonists in poor responders.
Hum Reprod. 2015 Oct; 30(10):2321-30.HR

Abstract

STUDY QUESTION

Do live birth rates differ between modified natural cycles (MNCs) and cycles using high-dose follicle stimulating hormone (HDFSH) with gonadotrophin-releasing hormone (GnRH) antagonist in poor responder patients?

SUMMARY ANSWER

Live birth rates are significantly higher in MNC compared with HDFSH GnRH antagonist cycles in poor responder patients.

WHAT IS KNOWN ALREADY

Previous data on the efficiency of MNC in poor responders are very limited and suggest that MNC in vitro fertilization (IVF) does not offer a realistic solution for parenthood in these patients, since live birth rates are disappointingly low. To date, no studies exist comparing MNC with HDFSH stimulation protocols in poor responders.

STUDY DESIGN, SIZE, DURATION

The present retrospective study included 161 MNCs (106 women in the MNC group) and 164 HDFSH antagonist cycles (136 women in the HDFSH group) performed between January 2008 and December 2013 at Eugonia Assisted Reproduction Unit. The patients included in the study had to fulfill the Bologna criteria for the definition of poor ovarian response.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Irrespective of their age, poor responder patients should have a diminished ovarian reserve as shown by low antral follicle count (≤5) and increased basal FSH (>12 IU/l), and one or more previous failed IVF cycles in which ≤3 oocytes were retrieved using a high gonadotrophin dose. Analysis was performed by adjusting for the non-independence of the data.

MAIN RESULTS AND THE ROLE OF CHANCE

The probability of live birth was significantly higher in the MNC when compared with the HDFSH group (OR: 4.01, 95% CI: 1.14-14.09), after adjusting for basal FSH, female age and cause of infertility, variables which were shown to be associated with the probability of live birth in univariable analysis. MNCs were characterized by significantly lower total gonadotrophin dose (490.0 ± 35.2 IU versus 2826.1 ± 93.4 IU, P < 0.001), lower estradiol concentrations (237.5 ± 12.3 pg/ml versus 487.3 ± 29.8 pg/ml, P < 0.001), fewer follicles present on the day of hCG (1.9 ± 0.1 versus 3.2 ± 0.2, P < 0.001), fewer oocytes retrieved (1.1 ± 0.01 versus 2.4 ± 0.1, P < 0.001), fewer oocytes fertilized (0.7 ± 0.1 versus 1.4 ± 0.1, P < 0.001), fewer embryos transferred (0.7 ± 0.1 versus 1.4 ± 0.1, P < 0.001), fewer good-quality embryos available (0.5 ± 0.1 versus 0.8 ± 0.1, P < 0.001) and fewer good-quality embryos transferred (0.5 ± 0.05 versus 0.8 ± 0.1, P < 0.001) compared with the HDFSH group. However, the proportion of cycles with at least one good-quality embryo transferred per started cycle was similar between the two groups compared (62.5, 95% CI: 52.7-72.3 versus 62.7, 95% CI: 53.0-72.5, respectively).

LIMITATIONS, REASONS FOR CAUTION

This is a retrospective comparison between MNC and HDFSH GnRH antagonist protocols in a large group of poor responder patients according to the Bologna criteria. Although the two groups compared were not imbalanced for all basic characteristics and multivariate analysis were performed to adjust for all known confounders, it cannot be excluded that non-apparent sources of bias might still be present. Future randomized controlled trials are necessary to verify the present findings.

WIDER IMPLICATIONS OF THE FINDINGS

Both MNC and HDFSH antagonist protocols offer very low chances of live birth in poor responder patients who fulfill the Bologna criteria. However, MNC-IVF is a more patient-friendly approach, with a higher probability of live birth compared with the HDFSH antagonist protocol. In this respect, the current data might be of help in counseling such patients, who do not wish to undergo oocyte donation, prior to abandoning treatment altogether and/or proceeding to adoption.

STUDY FUNDING/COMPETING INTERESTS

No funding was obtained. C.A.V. reports personal fees and non-financial support from Merck, Sharp and Dome, personal fees and non-financial support from Merck Serono, personal fees and non-financial support from IPSEN Hellas S.A. outside the submitted work. B.C.T. reports grants from Merck Serono, grants from Merck Sharp & Dohme, personal fees from IBSA, personal fees from Merck Sharp & Dohme and personal fees from Ovascience outside the submitted work .

Authors+Show Affiliations

Eugonia Assisted Reproduction Unit, 7 Ventiri Street, Athens 11528, Greece.Eugonia Assisted Reproduction Unit, 7 Ventiri Street, Athens 11528, Greece.Department of Women's and Children's Health, St George Hospital, School of Women's and Children's Health, University of New South Wales, Kogarah, NSW 2217, Australia.Eugonia Assisted Reproduction Unit, 7 Ventiri Street, Athens 11528, Greece.Eugonia Assisted Reproduction Unit, 7 Ventiri Street, Athens 11528, Greece.Unit for Human Reproduction, 1st Department of Obstetrics & Gynaecology, Papageorgiou General Hospital, Medical School, Aristotle University of Thessaloniki, Ring Road, Nea Efkarpia, Thessaloniki 56429, Greece.Unit for Human Reproduction, 1st Department of Obstetrics & Gynaecology, Papageorgiou General Hospital, Medical School, Aristotle University of Thessaloniki, Ring Road, Nea Efkarpia, Thessaloniki 56429, Greece stratis.kolibianakis@gmail.com.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26307091

Citation

Lainas, Trifon G., et al. "Live Birth Rates After Modified Natural Cycle Compared With High-dose FSH Stimulation Using GnRH Antagonists in Poor Responders." Human Reproduction (Oxford, England), vol. 30, no. 10, 2015, pp. 2321-30.
Lainas TG, Sfontouris IA, Venetis CA, et al. Live birth rates after modified natural cycle compared with high-dose FSH stimulation using GnRH antagonists in poor responders. Hum Reprod. 2015;30(10):2321-30.
Lainas, T. G., Sfontouris, I. A., Venetis, C. A., Lainas, G. T., Zorzovilis, I. Z., Tarlatzis, B. C., & Kolibianakis, E. M. (2015). Live birth rates after modified natural cycle compared with high-dose FSH stimulation using GnRH antagonists in poor responders. Human Reproduction (Oxford, England), 30(10), 2321-30. https://doi.org/10.1093/humrep/dev198
Lainas TG, et al. Live Birth Rates After Modified Natural Cycle Compared With High-dose FSH Stimulation Using GnRH Antagonists in Poor Responders. Hum Reprod. 2015;30(10):2321-30. PubMed PMID: 26307091.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Live birth rates after modified natural cycle compared with high-dose FSH stimulation using GnRH antagonists in poor responders. AU - Lainas,Trifon G, AU - Sfontouris,Ioannis A, AU - Venetis,Christos A, AU - Lainas,George T, AU - Zorzovilis,Ioannis Z, AU - Tarlatzis,Basil C, AU - Kolibianakis,Efstratios M, Y1 - 2015/08/25/ PY - 2015/03/06/received PY - 2015/07/16/accepted PY - 2015/8/27/entrez PY - 2015/8/27/pubmed PY - 2016/7/28/medline KW - Bologna criteria KW - GnRH antagonist protocol KW - live birth KW - modified natural cycle KW - poor responders SP - 2321 EP - 30 JF - Human reproduction (Oxford, England) JO - Hum Reprod VL - 30 IS - 10 N2 - STUDY QUESTION: Do live birth rates differ between modified natural cycles (MNCs) and cycles using high-dose follicle stimulating hormone (HDFSH) with gonadotrophin-releasing hormone (GnRH) antagonist in poor responder patients? SUMMARY ANSWER: Live birth rates are significantly higher in MNC compared with HDFSH GnRH antagonist cycles in poor responder patients. WHAT IS KNOWN ALREADY: Previous data on the efficiency of MNC in poor responders are very limited and suggest that MNC in vitro fertilization (IVF) does not offer a realistic solution for parenthood in these patients, since live birth rates are disappointingly low. To date, no studies exist comparing MNC with HDFSH stimulation protocols in poor responders. STUDY DESIGN, SIZE, DURATION: The present retrospective study included 161 MNCs (106 women in the MNC group) and 164 HDFSH antagonist cycles (136 women in the HDFSH group) performed between January 2008 and December 2013 at Eugonia Assisted Reproduction Unit. The patients included in the study had to fulfill the Bologna criteria for the definition of poor ovarian response. PARTICIPANTS/MATERIALS, SETTING, METHODS: Irrespective of their age, poor responder patients should have a diminished ovarian reserve as shown by low antral follicle count (≤5) and increased basal FSH (>12 IU/l), and one or more previous failed IVF cycles in which ≤3 oocytes were retrieved using a high gonadotrophin dose. Analysis was performed by adjusting for the non-independence of the data. MAIN RESULTS AND THE ROLE OF CHANCE: The probability of live birth was significantly higher in the MNC when compared with the HDFSH group (OR: 4.01, 95% CI: 1.14-14.09), after adjusting for basal FSH, female age and cause of infertility, variables which were shown to be associated with the probability of live birth in univariable analysis. MNCs were characterized by significantly lower total gonadotrophin dose (490.0 ± 35.2 IU versus 2826.1 ± 93.4 IU, P < 0.001), lower estradiol concentrations (237.5 ± 12.3 pg/ml versus 487.3 ± 29.8 pg/ml, P < 0.001), fewer follicles present on the day of hCG (1.9 ± 0.1 versus 3.2 ± 0.2, P < 0.001), fewer oocytes retrieved (1.1 ± 0.01 versus 2.4 ± 0.1, P < 0.001), fewer oocytes fertilized (0.7 ± 0.1 versus 1.4 ± 0.1, P < 0.001), fewer embryos transferred (0.7 ± 0.1 versus 1.4 ± 0.1, P < 0.001), fewer good-quality embryos available (0.5 ± 0.1 versus 0.8 ± 0.1, P < 0.001) and fewer good-quality embryos transferred (0.5 ± 0.05 versus 0.8 ± 0.1, P < 0.001) compared with the HDFSH group. However, the proportion of cycles with at least one good-quality embryo transferred per started cycle was similar between the two groups compared (62.5, 95% CI: 52.7-72.3 versus 62.7, 95% CI: 53.0-72.5, respectively). LIMITATIONS, REASONS FOR CAUTION: This is a retrospective comparison between MNC and HDFSH GnRH antagonist protocols in a large group of poor responder patients according to the Bologna criteria. Although the two groups compared were not imbalanced for all basic characteristics and multivariate analysis were performed to adjust for all known confounders, it cannot be excluded that non-apparent sources of bias might still be present. Future randomized controlled trials are necessary to verify the present findings. WIDER IMPLICATIONS OF THE FINDINGS: Both MNC and HDFSH antagonist protocols offer very low chances of live birth in poor responder patients who fulfill the Bologna criteria. However, MNC-IVF is a more patient-friendly approach, with a higher probability of live birth compared with the HDFSH antagonist protocol. In this respect, the current data might be of help in counseling such patients, who do not wish to undergo oocyte donation, prior to abandoning treatment altogether and/or proceeding to adoption. STUDY FUNDING/COMPETING INTERESTS: No funding was obtained. C.A.V. reports personal fees and non-financial support from Merck, Sharp and Dome, personal fees and non-financial support from Merck Serono, personal fees and non-financial support from IPSEN Hellas S.A. outside the submitted work. B.C.T. reports grants from Merck Serono, grants from Merck Sharp & Dohme, personal fees from IBSA, personal fees from Merck Sharp & Dohme and personal fees from Ovascience outside the submitted work . SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/26307091/Live_birth_rates_after_modified_natural_cycle_compared_with_high_dose_FSH_stimulation_using_GnRH_antagonists_in_poor_responders_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/dev198 DB - PRIME DP - Unbound Medicine ER -