Intrauterine injection of human chorionic gonadotropin before embryo transfer can improve in vitro fertilization-embryo transfer outcomes: a meta-analysis of randomized controlled trials

This meta-analysis reveals that infertile women treated with 500 IU hCG within 15 minutes before ET may achieve better IVF-ET outcomes.

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Volume 112, Issue 1, Pages 89–97.e1

Authors:

MingXia Gao, M.D., XiangYan Jiang, M.D., Bin Li, M.D., LiFei Li, M.D., MengTao Duan, M.Sc., XueHong Zhang, M.D., JinHui Tian, M.D., KeYan Qi, M.D.

Abstract:

Objective

To evaluate whether intrauterine injection of hCG before embryo transfer can improve IVF-ET outcomes.

Design

Meta-analysis.

Setting

Not applicable.

Patient(s)

Infertile women who underwent IVF-ET and received an intrauterine injection of hCG before ET.

Intervention(s)

Infertile women treated with or without intrauterine hCG injection before ET.

Main Outcome Measure(s)

The primary outcomes were live birth rate (LBR), ongoing pregnancy rate (OPR), and clinical pregnancy rate (CPR), and the secondary outcomes were implantation rate (IR) and miscarriage rate (MR). Odds ratios with 95% confidence intervals (CIs) and successful ET rates were pooled to determine the effects of hCG on IVF-ET outcomes.

Result(s)

Fifteen randomized controlled trials (RCTs) with a total of 2,763 participants were included. Infertile women in the experimental group (treated with intrauterine hCG injection before ET) exhibited significantly higher LBR (44.89% vs. 29.76%), OPR (48.09% vs. 33.42%), CPR (47.80% vs. 32.78%), and IR (31.64% vs. 22.52%) than those in the control group (intrauterine injection of placebo or no injection). Furthermore, MR was significantly lower (12.45% vs. 18.56%) in the experimental group than in the control group.

Conclusion(s)

The findings of this meta-analysis indicate that intrauterine injection of hCG can improve LBR, OPR, CPR, and IR after IVF-ET cycles. In addition, different timing and dosages of hCG administration may exert different effects on IVT-ET outcomes. Notably, infertile women treated with 500 IU hCG within 15 minutes before ET can achieve optimal IVF-ET outcomes.


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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

2 Comments

Go to the profile of Oscar Barbosa Duarte-Filho
Oscar Barbosa Duarte-Filho about 1 year ago

I read with great interest the systematic review of Gao & Jiang [1]  on the use of intrauterine hCG injection prior to embryo transfer in order to increase in vitro fertilization pregnancy rates. We were very excited about the possibility of resuming the use of this strategy, which until then was out of date due to previous systematic reviews showing inconsistent and conflicting result [2, 3].


I considered the Gao & Jiang study particularly interesting because it did the analysis of subgroups according to the dose of hCG used and the type of transfer, fresh or frozen, which is of great clinical relevance.


Regarding the time of intrauterine hCG application, the authors conclude that <15 minutes before transfer results in higher pregnancy rate than 6 hours and ≥48 hours. On this point, I have an issue. 


Considering that:


• The mechanism of action of hCG described by authors cited in the review would be to alter the expression of cytokines related to implantation, as well as to lead to extracellular matrix rupture and loss of tight-junction [4, 5];


• embryo implantation occurs approximately on the seventh day after fertilization;


I think that as important as the time interval between intrauterine hCG injection and the embryo transfer is the stage of the embryo at transfer, if cleavage or blastocyst, since this will determine the time interval between the two major biologic events: hCG injection signaling and embryo implantation.


From this, I would like to know if subgroup analysis could contemplate this variable (embryo stage at transfer)?


Oscar Duarte-Filho, M.D. 


References


[1] Gao M, Jiang X, Li B, Li L, Duan M, Zhang X, et al.: Intrauterine injection of human chorionic gonadotropin before embryo transfer can improve in vitro fertilization-embryo transfer outcomes: a meta-analysis of randomized controlled trials. Fertil Steril2019;112(1): 89-97.e81.


[2] Ye H, Hu J, He W, Zhang Y, Li C: The efficacy of intrauterine injection of human chorionic gonadotropin before embryo transfer in assisted reproductive cycles: Meta-analysis. J Int Med Res2015;43(6): 738-746.


[3] Osman A, Pundir J, Elsherbini M, Dave S, El-Toukhy T, Khalaf Y: The effect of intrauterine HCG injection on IVF outcome: a systematic review and meta-analysis. Reprod Biomed Online2016;33(3): 350-359.


[4] Tapia-Pizarro A, Argandoña F, Palomino WA, Devoto L: Human chorionic gonadotropin (hCG) modulation of TIMP1 secretion by human endometrial stromal cells facilitates extravillous trophoblast invasion in vitro. Hum Reprod2013;28(8): 2215-2227.


[5] Sacchi S, Sena P, Degli Esposti C, Lui J, La Marca A: Evidence for expression and functionality of FSH and LH/hCG receptors in human endometrium. J Assist Reprod Genet2018;35(9): 1703-1712.


 

Go to the profile of Oscar Barbosa Duarte-Filho
Oscar Barbosa Duarte-Filho about 1 year ago

I read with great interest the systematic review of Gao & Jiang [1]  on the use of intrauterine hCG injection prior to embryo transfer in order to increase in vitro fertilization pregnancy rates. We were very excited about the possibility of resuming the use of this strategy, which until then was out of date due to previous systematic reviews showing inconsistent and conflicting result [2, 3].


I considered the Gao & Jiang study particularly interesting because it did the analysis of subgroups according to the dose of hCG used and the type of transfer, fresh or frozen, which is of great clinical relevance.


Regarding the time of intrauterine hCG application, the authors conclude that <15 minutes before transfer results in higher pregnancy rate than 6 hours and ≥48 hours. On this point, I have an issue. 


Considering that:


• The mechanism of action of hCG described by authors cited in the review would be to alter the expression of cytokines related to implantation, as well as to lead to extracellular matrix rupture and loss of tight-junction [4, 5];


• embryo implantation occurs approximately on the seventh day after fertilization;


I think that as important as the time interval between intrauterine hCG injection and the embryo transfer is the stage of the embryo at transfer, if cleavage or blastocyst, since this will determine the time interval between the two major biologic events: hCG injection signaling and embryo implantation.


From this, I would like to know if subgroup analysis could contemplate this variable (embryo stage at transfer)?


Oscar Duarte-Filho, M.D. 


References


[1] Gao M, Jiang X, Li B, Li L, Duan M, Zhang X, et al.: Intrauterine injection of human chorionic gonadotropin before embryo transfer can improve in vitro fertilization-embryo transfer outcomes: a meta-analysis of randomized controlled trials. Fertil Steril2019;112(1): 89-97.e81.


[2] Ye H, Hu J, He W, Zhang Y, Li C: The efficacy of intrauterine injection of human chorionic gonadotropin before embryo transfer in assisted reproductive cycles: Meta-analysis. J Int Med Res2015;43(6): 738-746.


[3] Osman A, Pundir J, Elsherbini M, Dave S, El-Toukhy T, Khalaf Y: The effect of intrauterine HCG injection on IVF outcome: a systematic review and meta-analysis. Reprod Biomed Online2016;33(3): 350-359.


[4] Tapia-Pizarro A, Argandoña F, Palomino WA, Devoto L: Human chorionic gonadotropin (hCG) modulation of TIMP1 secretion by human endometrial stromal cells facilitates extravillous trophoblast invasion in vitro. Hum Reprod2013;28(8): 2215-2227.


[5] Sacchi S, Sena P, Degli Esposti C, Lui J, La Marca A: Evidence for expression and functionality of FSH and LH/hCG receptors in human endometrium. J Assist Reprod Genet2018;35(9): 1703-1712.