Abstract
Research question
Does follicular stimulation using human menopausal gonadotrophin (HMG) after pituitary
down-regulation by a GnRH agonist improve endometrial thickness (EMT) and clinical
outcomes of frozen-thawed embryo transfer (FET; using vitrified-warmed embryos) in
women with thin endometrium after intensified oestrogen administration (IOA)?
Design
This was a retrospective study. A total of 627 patients attempted 683 FET cycles with
at least one previous history of thin endometrium. None of the cycles reached over
7 mm EMT after using oral and vaginal oestradiol for more than 21 days (IOA protocol).
A total of 129 cycles proceeded with FET, 305 cycles were cancelled, and 249 cycles
involved administration of HMG following GnRH agonist pituitary down-regulation (GnRH
agonist + HMG protocol) for further endometrial preparation.
Results
EMT became significantly greater (7.18 ± 1.14 mm versus 6.13 ± 0.63 mm, P < 0.001) using GnRH agonist + HMG compared with previous IOA cycles, but this was
not related to serum oestrogen concentrations. A total of 213 cycles after the GnRH
agonist + HMG protocol proceeded with FET, showing a significantly increased clinical
pregnancy rate, implantation rate and live birth rate compared with those after IOA.
Conclusions
The GnRH agonist + HMG protocol for endometrial preparation in FET cycles improves
EMT in women with a thin endometrium after IOA and showed significantly better clinical
outcomes than IOA. The authors suggest that the GnRH agonist + HMG protocol should
be used for EMT that is less than 7 mm after there has been no optimal response to
IOA.
Keywords
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References
- The correlation between endometrial thickness and outcome of in vitro fertilization and embryo transfer (IVF-ET) outcome.Reprod. Bio. Endocrinol. 2008; 6: 37
- Insufficient Angiogenesis: Cause of Abnormally Thin Endometrium in Subfertile Patients?.Geburtshilfe und Frauenheilkunde. 2017; 77: 756-764
- Implantation failure of endometrial origin.Current Opinion in Obstetrics and Gynecology. 2018; 30: 229-236
- Human chorionic gonadotropin triggers angiogenesis via the modulation of endometrial stromal cell responsiveness to interleukin 1: a new possible mechanism underlying embryo implantation.Biology of reproduction. 2012; 87: 66
- The Impact of Endometrial Thickness on the Day of Human Chorionic Gonadotrophin (hCG) Administration on Ongoing Pregnancy Rate in Patients with Different Ovarian Response.PloS one. 2015; 10e0145703
- The impact of endometrial thickness (EMT) on the day of human chorionic gonadotropin (hCG) administration on pregnancy outcomes: a 5-year retrospective cohort analysis in Malaysia.Fertility research and practice. 2018; 4: 5
- Extended estrogen administration for women with thin endometrium in frozen-thawed in-vitro fertilization programs.Journal of assisted reproduction and genetics. 2006; 23: 337-342
- Apoptotic effects of high estradiol concentrations on endometrial glandular cells.The Journal of clinical endocrinology and metabolism. 2014; 99: E971-E980
- Factors influencing adverse perinatal outcomes in pregnancies achieved through use of in vitro fertilization.Fertility and sterility. 2006; 86: 1634-1641
- Recurrent implantation failure: definition and management.Reproductive biomedicine online. 2014; 28: 14-38
- Effects of growth hormone on pregnancy rates of patients with thin endometrium.Journal of endocrinological investigation. 2019; 42: 27-35
- Effect of adding human chorionic gonadotropin to frozen thawed embryo transfer cycles with history of thin endometrium.International journal of reproductive biomedicine. 2016; 14: 53-56
- Gonadotropin-releasing hormone agonist combined with hormone replacement therapy does not improve the reproductive outcomes of frozen-thawed embryo transfer cycle in elderly patients: a retrospective study.Reprod. Bio.l Endocrinol. 2020; 18: 73
- The relationship between endometrial thickness and outcome of medicated frozen embryo replacement cycles.Fertility and sterility. 2008; 89: 832-839
- Abnormal expression of estrogen receptor is associated with thin endometrium.Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology. 2019; 35: 544-547
- The influence of supraphysiologic estradiol levels on human nidation.Journal of assisted reproduction and genetics. 1995; 12: 406-412
- Effects of variations in serum estradiol concentrations on secretory endometrial development and function in experimentally induced cycles in normal women.Fertility and sterility. 2009; 92: 2058-2061
- Implantation Window and Angiogenesis.Journal of cellular biochemistry. 2017; 118: 4141-4151
- Efficacy of tocopherol and pentoxifylline combined therapy for women undergoing assisted reproductive treatment with poor endometrial development: a retrospective cohort study on 143 patients.Human fertility. 2021; 24: 367-375
- Controlled ovarian hyperstimulation does not adversely affect endometrial receptivity in in vitro fertilization cycles.Fertility and sterility. 2001; 76 (D. M.): 670-674
- Letrozole ovulation induction: an effective option in endometrial preparation for frozen-thawed embryo transfer.Archives of gynecology and obstetrics. 2014; 289: 687-693
- Evaluation of granulocyte colony-stimulating factor on the treatment of thin endometrium during frozen-thawed embryo transfer cycles: a retrospective cohort study.Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology. 2020; 36: 370-374
- Molecular aspects of direct LH/hCG effects on human endometrium–lessons from intrauterine microdialysis in the human female in vivo.Reproductive biology. 2001; 1: 10-19
- Management of thin endometrium in assisted reproduction: a clinical practice guideline from the Canadian Fertility and Andrology Society.Reproductive biomedicine online. 2019; 39: 49-62
- The impact of a thin endometrial lining on fresh and frozen-thaw IVF outcomes: an analysis of over 40 000 embryo transfers.Human reproduction. 2018; 33: 1883-1888
- Factors Associated with Effectiveness of Treatment and Reproductive Outcomes in Patients with Thin Endometrium Undergoing Estrogen Treatment.Chinese medical journal. 2015; 128: 3173-3177
- The incidence rate of unresponsive thin endometrium in frozen embryo transfer cycles: A case-series of therapy with granulocyte colony stimulating factor.Int J Reprod Biomed (Yazd). 2019; 17: 923-928
- Endometrial thickness influences neonatal birth weight in pregnancies with obstetric complications achieved after fresh IVF-ICSI cycles.Archives of gynecology and obstetrics. 2017; 296: 115-122
- Varying levels of serum estradiol do not alter the timing of the early endometrial secretory transformation.Human reproduction. 2020; 35: 1637-1647
- Follicular HCG endometrium priming for IVF patients experiencing resisting thin endometrium. A proof of concept study.Journal of assisted reproduction and genetics. 2013; 30: 1341-1345
- Hormonal induction of endometrial receptivity.Fertility and sterility. 2011; 96: 530-535
- Higher live birth rate with stimulated rather than artificial cycle for frozen-thawed embryo transfer.European journal of obstetrics, gynecology, and reproductive biology. 2019; 243: 144-149
- Embryo transfer strategy and therapeutic options in infertile patients with thin endometrium: a systematic review.Journal of assisted reproduction and genetics. 2019; 36: 2217-2231
- The presence of gonadotropin receptors in nonpregnant human uterus, human placenta, fetal membranes, and decidua.The Journal of clinical endocrinology and metabolism. 1990; 70: 421-430
- Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.Fertility and sterility. 2004; 81: 19-25
- The effect of endometrial thickness on pregnancy outcomes of frozen-thawed embryo transfer cycles which underwent hormone replacement therapy.PloS one. 2020; 15e0239120
- Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen-thawed embryo transfer in normal responders.Fertility and sterility. 2011; 96: 344-348
- Ovarian stimulation and exogenous progesterone affect the endometrial miR-16-5p, VEGF protein expression, and angiogenesis.Microvascular Research. 2021; 133104074
- Endometrial but not Ovarian Response is Associated With Clinical Outcomes and can be Improved by Prolonged Pituitary Downregulation in Patients With Thin and Medium Endometrium.Reproductive sciences. 2019; 26: 1409-1416
- Endocrine and clinical effects of micronized estradiol administered vaginally or orally.Fertility and sterility. 2001; 75: 200-202
- Endometrial Vascularization Characterized by Optical Coherence Tomography and Immunohistochemistry in Women Undergoing In Vitro Fertilization-Embryo Transfer Treatment.Medicina (Kaunas). 2019; 55: 81
- Investigation of platelet-rich plasma in increasing proliferation and migration of endometrial mesenchymal stem cells and improving pregnancy outcome of patients with thin endometrium.Journal of cellular biochemistry. 2018; : 1-9
- Endometrial thickness affects the outcome of in vitro fertilization and embryo transfer in normal responders after GnRH antagonist administration.Reproductive biology and endocrinology. 2014; 12: 96
- A study on the estrogen receptor alpha gene polymorphism and its expression in thin endometrium of unknown etiology.Gynecol. Obstet. Invest. 2012; 74: 13-20
- Endometrial thickness as a predictor of pregnancy outcomes in 10787 fresh IVF–ICSI cycles.Reproductive biomedicine online. 2016; 33: 197-205
- Letrozole use during frozen embryo transfer cycles in women with polycystic ovary syndrome.Fertility and sterility. 2019; 112: 371-377
- Effect of endometrial thickness on birthweight in frozen embryo transfer cycles: an analysis including 6181 singleton newborns.Human reproduction. 2019; 34: 1707-1715
Biography
Peiyu Wang, MD, received her medical degree in obstetrics and gynaecology in 2010 and has worked at the Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, China, for 12 years. Her special research interests are treatment for thin endometrium, recurrent miscarriage and repeated implantation failure.
Key message
Follicular stimulation using human menopausal gonadotrophin after pituitary down-regulation by gonadotrophin-releasing hormone agonists can be used for endometrial preparation in frozen-thawed embryo transfer cycles to improve endometrial thickness and clinical outcomes when endometrial thickness is less than 7 mm after intensified oestrogen administration.
Article info
Publication history
Published online: December 07, 2022
Accepted:
December 2,
2022
Received in revised form:
November 29,
2022
Received:
September 18,
2022
Declaration: The authors report no financial or commercial conflicts of interest.Identification
Copyright
© 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
