Impact of Plasmatic Progesterone on the Day of Frozen Embryo Transfer in Hormone-induced Cycles

Abstract

Objective To establish a relationship between serum progesterone values on the day of frozen blastocyst transfer in hormone-replaced cycles with the probability of pregnancy, miscarriage or delivery.

Methods This was an ambispective observational study including all frozen-thawed embryo transfer cycles performed at our department following in vitro fecundation from May 2018 to June 2019. The outcomes evaluated were β human chorionic gonadotropin (β-hCG)-positive pregnancy and delivery. Groups were compared according to the level of serum progesterone on the day of embryo transfer: the 1^st quartile of progesterone was compared against the other quartiles and then the 2^nd and 3^rd quartiles against the 4^th quartile.

Results A total of 140 transfers were included in the analysis: 87 with β-HCG > 10 IU/L (62%), of which 50 (36%) delivered and 37 had a miscarriage (42%). Women with lower progesterone levels (< 10.7ng/mL) had a trend toward higher β-HCG-positive (72 versus 59%; p > 0.05), lower delivery (26 versus 39%; p > 0.05) and higher miscarriage rates (64 versus 33%; p < 0.01). Comparing the middle quartiles (P25–50) with those above percentiles 75, the rate of pregnancy was similar (60 versus 57%; p > 0.05), although there was a trend toward a higher number of deliveries (43 versus 31%; p > 0.05) and a lower number of miscarriages (28 versus 45%; p > 0.05). These differences were not statistically significant.

Conclusion There were no differences in pregnancy and delivery rates related with the progesterone level when measured in the transfer day. The miscarriage rate was higher in the 1^st quartile group.

Resumo

Objetivo Avaliar se existe alguma relação entre os valores plasmáticos de progesterona no dia da transferência de um blastocisto desvitrificado em ciclos hormonalmente substituídos e a taxa de gravidez, aborto ou nascido vivo.

Métodos Estudo observacional, ambispectivo, incluindo todos os ciclos de transferência de blastocistos congelados no nosso departamento, entre maio de 2018 e junho de 2019. Avaliou-se a taxa de gravidez e de nascidos vivos após 24 semanas de gestação. Os grupos foram comparados de acordo com os valores de progesterona plasmáticos dosados no dia da transferência do blastocisto: comparou-se o 1° quartil com os outros e depois os 2° e 3° quartis com o 4°.

Resultados Avaliaram-se 140 transferências: 87 com β gonadotrofina coriônica humana (β-HCG) > 10 IU/L (62%), 50 das quais terminaram em nascido vivo (36% do total), enquanto 37 tiveram um aborto (42% das gravidezes). Verificou-se uma tendência para menor número de recém-nascidos nas transferências com níveis de progesterona no 1° quartil (< 10.7ng/mL) (26 versus 39%; p > 0.05) e um maior número de abortos (64 versus 33%; p < 0.01). Comparando o 2° e 3° quartis com o 4°, verificou-se que nos casos em que a progesterona estava acima do percentil 75, apesar de uma taxa de gravidez semelhante (60 versus 57%; p > 0.05), houve uma tendência para uma maior taxa de nascidos vivos (43 versus 31%; p > 0.05) e menor número de abortos (28 versus 45%; p > 0.05) abaixo do percentil 75. Estas diferenças não foram estatisticamente significativas.

Conclusão Não se verificaram diferenças estatisticamente significativas para taxa de gravidez e de nascido vivo. A taxa de aborto foi maior no primeiro quartil.

Keywords

progesterone - blastocyst - frozen embryo transfer - artificial cycle - miscarriage - delivery

Palavras-chave

progesterona - blastocisto - transferência de embrião congelado - ciclo artificial - aborto - parto

Contributions

All authors were involved in the design and interpretation of the analyses; they contributed to the writing and read and approved the final manuscript.

Publication History

Received: 30 June 2020

Accepted: 23 July 2021

Article published online:
21 September 2021

• References

• 1 Rienzi L, Gracia C, Maggiulli R, LaBarbera AR, Kaser DJ, Ubaldi FM. et al. Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance. Hum Reprod Update 2017; 23 (02) 139-155
• 2 De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T. et al; European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). ART in Europe, 2014: results generated from European registries by ESHRE: The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Hum Reprod 2018; 33 (09) 1586-1601
• 3 Devroey P, Polyzos NP, Blockeel C. An OHSS-Free Clinic by segmentation of IVF treatment. Hum Reprod 2011; 26 (10) 2593-2597
• 4 Coates A, Kung A, Mounts E, Hesla J, Bankowski B, Barbieri E. et al. Optimal euploid embryo transfer strategy, fresh versus frozen, after preimplantation genetic screening with next generation sequencing: a randomized controlled trial. Fertil Steril 2017; 107 (03) 723-730.e3
• 5 Groenewoud ER, Cohlen BJ, Macklon NS. Programming the endometrium for deferred transfer of cryopreserved embryos: hormone replacement versus modified natural cycles. Fertil Steril 2018; 109 (05) 768-774
• 6 Yarali H, Polat M, Mumusoglu S, Yarali I, Bozdag G. Preparation of endometrium for frozen embryo replacement cycles: a systematic review and meta-analysis. J Assist Reprod Genet 2016; 33 (10) 1287-1304
• 7 Blesa D, Ruiz-Alonso M, Simón C. Clinical management of endometrial receptivity. Semin Reprod Med 2014; 32 (05) 410-413
• 8 El-Toukhy T, Coomarasamy A, Khairy M, Sunkara K, Seed P, Khalaf Y. et al. The relationship between endometrial thickness and outcome of medicated frozen embryo replacement cycles. Fertil Steril 2008; 89 (04) 832-839
• 9 Gellersen B, Brosens JJ. Cyclic decidualization of the human endometrium in reproductive health and failure. Endocr Rev 2014; 35 (06) 851-905
• 10 van der Linden M, Buckingham K, Farquhar C, Kremer JA, Metwally M. Luteal phase support for assisted reproduction cycles. Cochrane Database Syst Rev 2015; (07) CD009154
• 11 Casper RF, Yanushpolsky EH. Optimal endometrial preparation for frozen embryo transfer cycles: window of implantation and progesterone support. Fertil Steril 2016; 105 (04) 867-872
• 12 Griesinger G, Tournaye H, Macklon N, Petraglia F, Arck P, Blockeel C. et al. Dydrogesterone: pharmacological profile and mechanism of action as luteal phase support in assisted reproduction. Reprod Biomed Online 2019; 38 (02) 249-259
• 13 Rashidi BH, Ghazizadeh M, Tehrani Nejad ES, Bagheri M, Gorginzadeh M. Oral dydrogesterone for luteal support in frozen-thawed embryo transfer artificial cycles: a pilot randomized controlled trial. Asian Pac J Reprod 2016; 5 (06) 490-494
• 14 Gaggiotti-Marre S, Martinez F, Coll L, Garcia S, Álvarez M, Parriego M. et al. Low serum progesterone the day prior to frozen embryo transfer of euploid embryos is associated with significant reduction in live birth rates. Gynecol Endocrinol 2019; 35 (05) 439-442
• 15 Labarta E, Mariani G, Holtmann N, Celada P, Remohí J, Bosch E. Low serum progesterone on the day of embryo transfer is associated with a diminished ongoing pregnancy rate in oocyte donation cycles after artificial endometrial preparation: a prospective study. Hum Reprod 2017; 32 (12) 2437-2442
• 16 Kofinas JD, Blakemore J, McCulloh DH, Grifo J. Serum progesterone levels greater than 20 ng/dl on day of embryo transfer are associated with lower live birth and higher pregnancy loss rates. J Assist Reprod Genet 2015; 32 (09) 1395-1399
• 17 ALPHA Scientists In Reproductive Medicine, ESHRE Special Interest Group Embryology. Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Reprod Biomed Online 2011; 22 (06) 632-646
• 18 Brady PC, Kaser DJ, Ginsburg ES, Ashby RK, Missmer SA, Correia KF. et al. Serum progesterone concentration on day of embryo transfer in donor oocyte cycles. J Assist Reprod Genet 2014; 31 (05) 569-575
• 19 Yovich JL, Conceicao JL, Stanger JD, Hinchliffe PM, Keane KN. Mid-luteal serum progesterone concentrations govern implantation rates for cryopreserved embryo transfers conducted under hormone replacement. Reprod Biomed Online 2015; 31 (02) 180-191
• 20 Basnayake SK, Volovsky M, Rombauts L, Osianlis T, Vollenhoven B, Healey M. Progesterone concentrations and dosage with frozen embryo transfers - What's best?. Aust N Z J Obstet Gynaecol 2018; 58 (05) 533-538
• 21 Alsbjerg B, Thomsen L, Elbaek HO, Laursen R, Povlsen BB, Haahr T. et al. Progesterone levels on pregnancy test day after hormone replacement therapy-cryopreserved embryo transfer cycles and related reproductive outcomes. Reprod Biomed Online 2018; 37 (05) 641-647
• 22 Cédrin-Durnerin I, Isnard T, Mahdjoub S, Sonigo C, Seroka A, Comtet M. et al. Serum progesterone concentration and live birth rate in frozen-thawed embryo transfers with hormonally prepared endometrium. Reprod Biomed Online 2019; 38 (03) 472-480
• 23 Labarta ED, Mariani G, Paolelli S. et al. O-173: A large prospective trial in unselected population confirms that low serum progesterone on the day of embryo transfer impairs pregnancy outcome in artificial cycles. Hum Reprod. 2019 ;34 Suppl 1:82. Abstract Book - ESHRE 2019–Vienna, Austria, 2019 Jun 23–26.
• 24 Hull MG, Savage PE, Bromham DR, Ismail AA, Morris AF. The value of a single serum progesterone measurement in the midluteal phase as a criterion of a potentially fertile cycle (“ovulation”) derived form treated and untreated conception cycles. Fertil Steril 1982; 37 (03) 355-360
• 25 Jordan J, Craig K, Clifton DK, Soules MR. Luteal phase defect: the sensitivity and specificity of diagnostic methods in common clinical use. Fertil Steril 1994; 62 (01) 54-62
• 26 Murray MJ, Meyer WR, Zaino RJ, Lessey BA, Novotny DB, Ireland K. et al. A critical analysis of the accuracy, reproducibility, and clinical utility of histologic endometrial dating in fertile women. Fertil Steril 2004; 81 (05) 1333-1343
• 27 Lessey BA. Assessment of endometrial receptivity. Fertil Steril 2011; 96 (03) 522-529
• 28 Nahoul K, Dehennin L, Jondet M, Roger M. Profiles of plasma estrogens, progesterone and their metabolites after oral or vaginal administration of estradiol or progesterone. Maturitas 1993; 16 (03) 185-202
• 29 Miles RA, Paulson RJ, Lobo RA, Press MF, Dahmoush L, Sauer MV. Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes: a comparative study. Fertil Steril 1994; 62 (03) 485-490
• 30 Paulson RJ, Collins MG, Yankov VI. Progesterone pharmacokinetics and pharmacodynamics with 3 dosages and 2 regimens of an effervescent micronized progesterone vaginal insert. J Clin Endocrinol Metab 2014; 99 (11) 4241-4249