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Ovarian response to controlled ovarian hyperstimulation: what does serum FSH say?
Hum Reprod. 2017 08 01; 32(8):1701-1709.HR

Abstract

STUDY QUESTION

Do serum FSH levels on day of hCG trigger differ between women with a poor, normal or hyper response to a fixed daily dose of 150 IU recombinant FSH (rFSH)?

SUMMARY ANSWER

There is no consistent relationship between ovarian response and serum FSH levels on day of hCG trigger in a 150 IU fixed dose treatment protocol.

WHAT IS KNOWN ALREADY

When ovarian response to stimulation for IVF/ICSI is suboptimal, the FSH dose is often adjusted in a subsequent cycle, thereby assuming that serum FSH levels were inadequate for optimal stimulation.

STUDY DESIGN, SIZE, DURATION

Nested cohort study within a randomized controlled trial conducted at the University Medical Centre Utrecht between March 2009 and July 2011. Blood was drawn from 124 women on cycle Day 2 and on day of hCG triggering. Serum FSH level was determined by the Beckman-Coulter Unicel DXi800 chemiluminescence assay. In order to detect a difference of 2 IU/L between poor, normal and hyper responders, a total of 64 participants (16 poor, 32 normal and 16 hyper responders) would provide 80% power, assuming a standard deviation of 2 and an alpha of 0.05.

PARTICIPANTS, SETTING, METHODS

Women aged ≤39 years with a regular cycle and fixed FSH dose of 150 IU. Exclusion criteria: BMI > 32 kg/m2 and >2 previous unsuccessful IVF/ICSI cycles. The primary outcome measure was serum FSH level on day of triggering.

MAIN RESULTS AND THE ROLE OF CHANCE

Median [range] body weight was 70.0 kg [55.0-85.6], 68.0 kg [52.0-94] and 60.6 kg [51.0-78.0] for poor (n = 16), normal (n = 94) and hyper (n = 17) responders, respectively. Mean (SD) serum FSH levels on day of triggering were 9.5 IU/L (2.4) in poor, 10.4 IU/L (2.3) in normal and 11.5 IU/L (2.2) in hyper responders. Serum FSH levels on day of hCG in poor responders differed significantly as compared to those in hyper responders (P = 0.03).

LIMITATIONS, REASONS FOR CAUTION

The number of retrieved oocytes is only minimally determined by serum FSH level on the day of hCG trigger. After correction for age, body weight, basal serum FSH and basal anti-Mullerian hormone the correlation between serum FSH level on the day of hCG and ovarian response regarding the number of retrieved oocytes disappeared.

WIDER IMPLICATIONS OF THE FINDINGS

The current study shows that a poor response is not related to inadequate serum FSH levels per se. One could therefore question whether increasing the rFSH dose in women with a suboptimal response is meaningful. In women with a hyper response, however, lowering the dose of rFSH in a subsequent IVF cycle may lead to lower serum FSH levels and thereby mitigate ovarian response and improve safety of the IVF treatment. As this was not a dose-response study, future research should assess whether dose adjustments benefit the poor and hyper responder.

STUDY FUNDING/COMPETING INTEREST(S)

No external funds were obtained for this study. S.C.O, T.C.v.T., O.H., H.L.T., E.G.W.M.L., C.B.L. and M.J.C.E. have nothing to disclose. F.J.M.B. receives monetary compensation: member of the external advisory board for Merck Serono and Ferring, the Netherlands; educational activities for Ferring BV, the Netherlands; consultancy work for Gedeon Richter, Belgium; strategic cooperation with Roche on automated AMH assay development and research cooperation with Ansh Labs.

Authors+Show Affiliations

Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA Utrecht, the Netherlands.Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA Utrecht, the Netherlands.Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA Utrecht, the Netherlands. Department of Reproductive Medicine, Radboud University Medical Centre Nijmegen, Geert Grooteplein-Zuid 10, PO Box 9101, 6500 HB Nijmegen, the Netherlands.Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA Utrecht, the Netherlands.Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA Utrecht, the Netherlands.Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA Utrecht, the Netherlands.Department of Obstetrics and Gynaecology, VU Medical Centre, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, the Netherlands.Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA Utrecht, the Netherlands.

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

28854580

Citation

Oudshoorn, Simone C., et al. "Ovarian Response to Controlled Ovarian Hyperstimulation: what Does Serum FSH Say?" Human Reproduction (Oxford, England), vol. 32, no. 8, 2017, pp. 1701-1709.
Oudshoorn SC, van Tilborg TC, Hamdine O, et al. Ovarian response to controlled ovarian hyperstimulation: what does serum FSH say? Hum Reprod. 2017;32(8):1701-1709.
Oudshoorn, S. C., van Tilborg, T. C., Hamdine, O., Torrance, H. L., Eijkemans, M. J. C., Lentjes, E. G. W. M., Lambalk, C. B., & Broekmans, F. J. M. (2017). Ovarian response to controlled ovarian hyperstimulation: what does serum FSH say? Human Reproduction (Oxford, England), 32(8), 1701-1709. https://doi.org/10.1093/humrep/dex222
Oudshoorn SC, et al. Ovarian Response to Controlled Ovarian Hyperstimulation: what Does Serum FSH Say. Hum Reprod. 2017 08 1;32(8):1701-1709. PubMed PMID: 28854580.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ovarian response to controlled ovarian hyperstimulation: what does serum FSH say? AU - Oudshoorn,Simone C, AU - van Tilborg,Theodora C, AU - Hamdine,Ouijdane, AU - Torrance,Helen L, AU - Eijkemans,Marinus J C, AU - Lentjes,Eef G W M, AU - Lambalk,Cornelis B, AU - Broekmans,Frank J M, PY - 2016/09/27/received PY - 2017/05/26/accepted PY - 2017/9/1/entrez PY - 2017/9/1/pubmed PY - 2018/5/22/medline KW - IVF/ICSI KW - controlled ovarian stimulation KW - ovarian response KW - recombinant FSH KW - serum FSH level SP - 1701 EP - 1709 JF - Human reproduction (Oxford, England) JO - Hum. Reprod. VL - 32 IS - 8 N2 - STUDY QUESTION: Do serum FSH levels on day of hCG trigger differ between women with a poor, normal or hyper response to a fixed daily dose of 150 IU recombinant FSH (rFSH)? SUMMARY ANSWER: There is no consistent relationship between ovarian response and serum FSH levels on day of hCG trigger in a 150 IU fixed dose treatment protocol. WHAT IS KNOWN ALREADY: When ovarian response to stimulation for IVF/ICSI is suboptimal, the FSH dose is often adjusted in a subsequent cycle, thereby assuming that serum FSH levels were inadequate for optimal stimulation. STUDY DESIGN, SIZE, DURATION: Nested cohort study within a randomized controlled trial conducted at the University Medical Centre Utrecht between March 2009 and July 2011. Blood was drawn from 124 women on cycle Day 2 and on day of hCG triggering. Serum FSH level was determined by the Beckman-Coulter Unicel DXi800 chemiluminescence assay. In order to detect a difference of 2 IU/L between poor, normal and hyper responders, a total of 64 participants (16 poor, 32 normal and 16 hyper responders) would provide 80% power, assuming a standard deviation of 2 and an alpha of 0.05. PARTICIPANTS, SETTING, METHODS: Women aged ≤39 years with a regular cycle and fixed FSH dose of 150 IU. Exclusion criteria: BMI > 32 kg/m2 and >2 previous unsuccessful IVF/ICSI cycles. The primary outcome measure was serum FSH level on day of triggering. MAIN RESULTS AND THE ROLE OF CHANCE: Median [range] body weight was 70.0 kg [55.0-85.6], 68.0 kg [52.0-94] and 60.6 kg [51.0-78.0] for poor (n = 16), normal (n = 94) and hyper (n = 17) responders, respectively. Mean (SD) serum FSH levels on day of triggering were 9.5 IU/L (2.4) in poor, 10.4 IU/L (2.3) in normal and 11.5 IU/L (2.2) in hyper responders. Serum FSH levels on day of hCG in poor responders differed significantly as compared to those in hyper responders (P = 0.03). LIMITATIONS, REASONS FOR CAUTION: The number of retrieved oocytes is only minimally determined by serum FSH level on the day of hCG trigger. After correction for age, body weight, basal serum FSH and basal anti-Mullerian hormone the correlation between serum FSH level on the day of hCG and ovarian response regarding the number of retrieved oocytes disappeared. WIDER IMPLICATIONS OF THE FINDINGS: The current study shows that a poor response is not related to inadequate serum FSH levels per se. One could therefore question whether increasing the rFSH dose in women with a suboptimal response is meaningful. In women with a hyper response, however, lowering the dose of rFSH in a subsequent IVF cycle may lead to lower serum FSH levels and thereby mitigate ovarian response and improve safety of the IVF treatment. As this was not a dose-response study, future research should assess whether dose adjustments benefit the poor and hyper responder. STUDY FUNDING/COMPETING INTEREST(S): No external funds were obtained for this study. S.C.O, T.C.v.T., O.H., H.L.T., E.G.W.M.L., C.B.L. and M.J.C.E. have nothing to disclose. F.J.M.B. receives monetary compensation: member of the external advisory board for Merck Serono and Ferring, the Netherlands; educational activities for Ferring BV, the Netherlands; consultancy work for Gedeon Richter, Belgium; strategic cooperation with Roche on automated AMH assay development and research cooperation with Ansh Labs. SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/28854580/Ovarian_response_to_controlled_ovarian_hyperstimulation:_what_does_serum_FSH_say L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/dex222 DB - PRIME DP - Unbound Medicine ER -