Vitirifiye embriyo transfer sikluslarında artifisyel endometrial hazırlıkta östrojen takviyesinin kısa süre kullanımı ile reprodüktif sonuçlar arasındaki ilişki

Yıl 2019, , 210 - 213, 15.12.2019

Aysen Boza , Gülümser Ece Aksakal Mehmet Ceyhan Oğuzhan Bulduk Başak Balaban Bülent Urman

https://doi.org/10.16948/zktipb.639155

Öz

Amaç: Vitrifiye embriyo transfer (VET) sikluslarında progesteron (P) desteği öncesi östradiyol (Ö) kullanım süresinin canlı doğum oranını (CDO) etkileyip etkilemediğini değerlendirmek  

Gereçler ve Yöntem: Bu retrospektif kohort çalışma, Ekim 2015 ve Ekim 2017 arasında Amerikan Hastanesi Üremeye Yardımcı Teknikler Ünitesi’nde GnRH agonist uygulamasız artifisyel endometriyum hazırlığı ile tek blastokist transferi yapılan tüm hastaları kapsamaktadır. Sadece G1 ve G2 iyi kalitede blastokistler dondurulmuştur. >43 yaş olanlar, tedavi siklus kayıtlarında eksik verileri olan veya takipten çıkan hastalar çalışma dışı bırakılmıştır. Tüm hastalara âdetin 2. günü 6 mg sabit dozdan oral Ö tedavisi başlanmıştır. Östradiyol kullanım süresi embriyo transfer (ET) günü planlamasına göre 8 ile 14 gün arası değişmektedir. Toplamda 241 hastanın VET siklusu Ö kullanım sürelerine göre (Grup 1: <12 gün, n=105; Grup 2: ³12 gün, n=136) analiz edilmiştir. Çalışmanın primer sonuç değişkeni CDO’ dır.  

Bulgular: Toplam 241 VET siklusundaki P kullanımı öncesi E kullanım süresi: 8 gün (%3), 9 gün (%8), 10 gün (%16), 11 gün (%16.5), 12 gün (%22.5), 13 gün (%20.5), 14 gün (%13.5) şeklinde dağılım göstermektedir. Östradiyol takviyesinin 12 günün altında kullanımının 12 gün üzerinde kullanımına kıyasla CDO üzerine anlamlı etkisi yoktur (OR=1.25; %95 CI [0.75-2.1], p=0.38). Klinik gebelik, erken ve fetal kayıp oranları da gruplar arasında benzerdir. Ortalama endometrial kalınlık gruplar arasında benzerdir (9.5mm). Östradiyol takviyesinin reprodüktif sonuçlarla ilişkisi her gün için ayrı ayrı değerlendirildiğinde de anlamlı bir fark saptanmamıştır 

Sonuç: Vitrifiye embriyo transfer sikluslarında genel kabul görenden daha kısa östradiyol kullanımı canlı doğum oranlarını etkilememekte, abort riskini artırmamaktadır. Bu durum test edilmemiş ancak kuvvetle kabül görmüş bu protokolü sorgulanır kılmaktadır    

Anahtar Kelimeler

blastokist, vitrifiye, embriyo transferi, östrojen, endometriyum

Effect of shorter duration of estrogen replacement on the outcome of vitrified warmed embryo transfer cycles

Öz

Objective: To evaluate the effect of a shorter duration of estradiol (E) exposure prior to progesterone (P) administration on live birth rate (LBR) in vitrified warmed embryo transfer (VWET) cycles. 

Materials-Methods: A retrospective cohort study was conducted in the American Hospital (Koc University affiliated private hospital) between October 2015 and October 2017. All VWET cycles with a single blastocyst transfer using artificial endometrial preparation without GnRH agonist pretreatment were included. Only G1 and G2 good quality blastocysts had been cryopreserved. Women >43 years of age, treatment cycles with incomplete data and women who were lost to follow-up were excluded.

Participants/material, setting, methods: All women received oral E treatment starting on day 2 of menstrual bleeding in a fixed dose of 6mg/day. The duration of E administration varied from 8 to 14 days due to concerns regarding embryo transfer scheduling. A total of 241 patients with vitrified warmed single blastocyst transfer cycles were analyzed according to the duration of E administration (Group 1: <12 days, n=105; Group 2: ³12 days, n=136). The main outcome measure was LBR per transfer.  

Results: Among a total of 241 patients with vitrified warmed blastocyst transfers, E exposure prior to P supplementation was as follows: 8 days (3%), 9 days (8%), 10 days (16%), 11 days (16.5%), 12 days (22.5%), 13 days (20.5%), 14 days (13.5%). LBR was not significantly affected when the E treatment was administered for less than 12 days (OR=1.25; 95%CI [0.75-2.1], p=0.38). Mean endometrial thickness was similar among the groups (9.5mm). When the patients were sub-divided according to the duration of E treatment, primary and secondary outcomes were likewise similar. 

Conclusion: Shorter than the normally accepted duration of E administration yields similar LBRs in VWET cycles, thus questioning the need to adhere strictly to an untested protocol. 

Anahtar Kelimeler

blastocyst, vitrification, embryo transfer, estrogen, endometrium

Kaynakça

• Balaban, B., Yakin, K., & Urman, B. (2006). Randomized comparison of two different blastocyst grading systems. Fertility and Sterility. https://doi.org/10.1016/j.fertnstert.2005.11.013
• Borini, A., Prato, L. D., Bianchi, L., Violini, F., Cattoli, M., & Flamigni, C. (2001). Effect of duration of estradiol replacement on the outcome of oocyte donation. Journal of Assisted Reproduction and Genetics.
• Bourdon, M., Santulli, P., Kefelian, F., Vienet-Legue, L., Maignien, C., Pocate-Cheriet, K., … Chapron, C. (2018). Prolonged estrogen (E2) treatment prior to frozen-blastocyst transfer decreases the live birth rate. Human Reproduction. https://doi.org/10.1093/humrep/dey041
• Cobo, A., De Los Santos, M. J., Castellò, D., Gámiz, P., Campos, P., & Remohí, J. (2012). Outcomes of vitrified early cleavage-stage and blastocyst-stage embryos in a cryopreservation program: Evaluation of 3,150 warming cycles. Fertility and Sterility. https://doi.org/10.1016/j.fertnstert.2012.07.1107
• Ghobara, T., Gelbaya, T. A., & Ayeleke, R. O. (2017). Cycle regimens for frozen-thawed embryo transfer. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.CD003414.pub3
• Kupka, M. S., D’Hooghe, T., Ferraretti, A. P., De Mouzon, J., Erb, K., Castilla, J. A., … Goossens, V. (2016). Assisted reproductive technology in Europe, 2011: Results generated from European registers by ESHRE. Human Reproduction. https://doi.org/10.1093/humrep/dev319
• Ma, W. ge, Song, H., Das, S. K., Paria, B. C., & Dey, S. K. (2003). Estrogen is a critical determinant that specifies the duration of the window of uterine receptivity for implantation. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.0530162100
• Makker, A., & Singh, M. M. (2006). Endometrial receptivity: Clinical assessment in relation to fertility, infertility, and antifertility. Medicinal Research Reviews. https://doi.org/10.1002/med.20061
• Michalas, S., Loutradis, D., Drakakis, P., Kallianidis, K., Milingos, S., Deligeoroglou, E., & Aravantinos, D. (1996). A flexible protocol for the induction of recipient endometrial cycles in an oocyte donation programme. Human Reproduction. https://doi.org/10.1093/oxfordjournals.humrep.a019297
• Nastri, C. O., Nóbrega, B. N., Teixeira, D. M., Amorim, J., Diniz, L. M. M., Barbosa, M. W. P., … Martins, W. P. (2016). Low versus atmospheric oxygen tension for embryo culture in assisted reproduction: a systematic review and meta-analysis. Fertility and Sterility. https://doi.org/10.1016/j.fertnstert.2016.02.037
• Ramathal, C. Y., Bagchi, I. C., Taylor, R. N., & Bagchi, M. K. (2010). Endometrial decidualization: Of mice and men. Seminars in Reproductive Medicine. https://doi.org/10.1055/s-0029-1242989
• S.Sunkara, S.Seshadri, & T.El-Toukhy. (2011). The impact of the duration of estrogen supplementation on the outcome of medicated frozen-thawed embryo transfer (FET) cycles. Fertility and Sterility. https://doi.org/10.1016/j.fertnstert.2011.07.163 LK - http://julac.hosted.exlibrisgroup.com/openurl/HKPU_ALMA/HKPU_SERVICES_PAGE?sid=EMBASE&sid=EMBASE&issn=00150282&id=doi:10.1016%2Fj.fertnstert.2011.07.163&atitle=The+impact+of+the+duration+of+estrogen+supplementation+on+the+outcome+of+medicated+frozen-thawed+embryo+transfer+%28FET%29+cycles&stitle=Fertil.+Steril.&title=Fertility+and+Sterility&volume=96&issue=3&spage=S43&epage=&aulast=Sunkara&aufirst=S.K.&auinit=S.K.&aufull=Sunkara+S.K.&coden=&isbn=&pages=S43-
• Salamonsen, L. A., Nie, G., Hannan, N. J., & Dimitriadis, E. (2009). Society for reproductive biology founders lecture 2009. Preparing fertile soil: The importance of endometrial receptivity. Reproduction, Fertility and Development. https://doi.org/10.1071/RD09145
• Silver, R. M., Branch, D. W., Goldenberg, R., Iams, J. D., & Klebanoff, M. A. (2011). Nomenclature for pregnancy outcomes: Time for a change. Obstetrics and Gynecology. https://doi.org/10.1097/AOG.0b013e3182392977
• Simon, C., Domínguez, F., Valbuena, D., & Pellicer, A. (2003). The role of estrogen in uterine receptivity and blastocyst implantation. Trends in Endocrinology and Metabolism. https://doi.org/10.1016/S1043-2760(03)00084-5
• Van Den Abbeel, E., Balaban, B., Ziebe, S., Lundin, K., Cuesta, M. J. G., Klein, B. M., … Arce, J. C. (2013). Association between blastocyst morphology and outcome of single-blastocyst transfer. Reproductive BioMedicine Online. https://doi.org/10.1016/j.rbmo.2013.07.006
• Young, S. L. (2013). Oestrogen and progesterone action on endometrium: A translational approach to understanding endometrial receptivity. Reproductive BioMedicine Online. https://doi.org/10.1016/j.rbmo.2013.06.010
• Younis, J. S., Mordel, N., Lewin, A., Simon, A., Schenker, J. G., & Laufer, N. (1992). Artificial endometrial preparation for oocyte donation: The effect of estrogen stimulation on clinical outcome. Journal of Assisted Reproduction and Genetics. https://doi.org/10.1007/BF01203817