Manipulating the cellular immune environment of the post-ovulatory endometrium to improve fecundity in natural cycles

Presented by: Eric Chang, DO  & Rachel Cohen, DO

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Learning Outcomes: 

1. To familiarize the audience with the importance of inadequate uterine remodeling as a potential cause of unexplained infertility and implantation defects.

2. To familiarize the audience with the importance of the cellular immune system in the creation of spiral arterioles to allow nutrient exchange between mother and fetus.

3. To familiarize the audience in some methods used by the fetal-placental unit to counteract this increased cellular immune response from immune attack of the fetal semi-allograft.

4. To familiarize the audience with the possible role of endometrial irritation (scratch) in improving potential inadequate uterine re-modeling related to an inadequate cellular immune response.

5. To make the audience aware that the endometrial scratch can be a double-edged sword in that in some circumstances it can produce an excessive cellular immune response thus inhibiting successful implantation.

6. The objective is to present some data suggesting when to employ the endometrial scratch and when not to use it.

7. The objective is to learn when in the menstrual cycle is the best time to perform the procedure.

8. The objective is to suggest how long the effectiveness of the endometrial scratch is.

 

REFERENCES:

  1. Cohen RA, Check JH, Dougherty MP. Evidence that exposure to progesterone alone is a sufficient stimulus to cause a precipitous rise in the immunomodulatory protein the progesterone induced blocking factor (PIBF). J Assist Reprod Genet. 2016;33(2):221-229.
  2. Check JH. Progesterone therapy versus follicle maturing drugs--possible opposite effects on embryo implantationClin Exp Obstet Gynecol. 2002;29(1):5-10.
  3. Check JH, Cohen R. The role of progesterone and the progesterone receptor in human reproduction and cancerExpert Rev Endocrinol Metab. 2013;8(5):469-484. doi:10.1586/17446651.2013.827380
  4. J.H. Check, J. Liss, D. Check. The beneficial effect of luteal phase support on pregnancy rates in women with unexplained infertility. Clinical and Experimental Obstetrics & Gynecology, 2019, 46(3): 447-449.
  5. Check JH, Nowroozi K, Wu CH, Adelson HG, Lauer C: Ovulation‑inducing drugs versus progesterone therapy for infertility in patients with luteal phase defects. Int J Fertil 33(4):252‑256, 1988
  6. Check JH, Chase JS, Adelson HG, Teichman M, Rankin A: The efficacy of progesterone in achieving successful pregnancy: I. Prophylactic use during luteal phase in anovulatory women. Int J Fertil 32:135‑138, 1987.
  7. Check JH, Wu CH, Adelson HG: Decreased abortions in hMG induced pregnancies with prophylactic progesterone therapy (Progesterone added to hMG to reduce abortions). Int J Fertil 30:45‑57, 1985.
  8. Check JH, Chase JS, Nowroozi K, Wu CH, Adelson HG. Progesterone therapy to decrease first‑trimester spontaneous abortions in previous aborters. Int J Fertil 32:192‑193, 197-199, 1987.
  9. Check JH:  Debate:  Should progesterone supplements be used?  Yes.  Ed.  Howard J.A. Carp.  In:   Recurrent Pregnancy Loss - Causes, Controversies, and Treatment, Second Edition, Chapter 14, pgs 123-129., CRC Press 2014.
  10. Hameed A, Malik S, Regan L:  Debate:  Should progesterone supplements be used?  No. Ed. Howard J.A. Carp. In: Recurrent Pregnancy Loss – Causes, Controversies, and Treatment, Second Edition, Chapter 15, pgs 131-135, CRC Press 2014
  11. Coomarasamy et al.  A randomized trial of progesterone in women with recurrent miscarriages. NEJM 2015;373:2141-2148.
  12. Check JH.   Pros and cons of the use of progesterone to reduce miscarriage rates.  Clin Exp Obst Gyn 2018;45:652-655
  13. Yeko TR, Gorrill MJ, Hughes LH, Rodi IA, Buster JE, Sauer MV. Timely diagnosis of early ectopic pregnancy using a single blood progesterone measurementFertil Steril. 1987;48(6):1048-1050. doi:10.1016/s0015-0282(16)59607-1
  14. Choe JK, Check JH, Nowroozi K, Benveniste R, Barnea ER. Serum progesterone and 17‑hydroxyprogesterone in the diagnosis of ectopic pregnancies and the value of progesterone replacement in intrauterine pregnancies when serum progesterone levels are low. Gynecologic and Obstetric Investigation. 34:133‑138, 1992
  15. Check JH, Winkel CA, Check ML: Abortion rate in progesterone treated women presenting initially with low first trimester serum progesterone levels. The Am J Gyn Health IV(2):63/33‑34/64, March‑April, 1990.
  16. Stephenson MD, McQueen D, Winter M, Kliman HJ. Luteal start vaginal micronized progesterone improves pregnancy success in women with recurrent pregnancy lossFertil Steril. 2017;107(3):684-690.e2. doi:10.1016/j.fertnstert.2016.11.029
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  18. Check JH, Adelson HG, Davies E. Effect of clomiphene citrate therapy on post‑coital tests in successive treatment cycles including response to supplemental estrogen therapy. Arch Androl, 32:69‑76, 1994.
  19. Check JH, Aly J, Chang E.  Improving the chance of successful implantation – part I – embryo attachment to the endometrium and adequate trophoblast invasion.  Clin Exp Obst Gynecol 2016;43787-791.
  20. Barash A, Fieldust S, Sega L, et al.  Local injury of the endometrium doubles the incidence of successful pregnancies in patients undergoing in vitro fertilization.  Fertil Steril 2003;79:1317-22.
  21. Chang E t al.  An endometrial scratch can improve pregnancy rates in unexplained infertility given luteal phase progesterone support.  Clin Exp Obst Gyn, in press.
  22. Check JH, Choe JK, Cohen R, Summers-Chase D. Effect of taking a one time injection of one mg leuprolide acetate three days after embryo transfer on pregnancy outcome and level of first beta human chorionic gonadotropin (beta-hCG) level. Clin Exp Obstet Gynecol. 2015;42(5):568-570.
  23. Gibreel A, Badawy A, El-Refai W, El-Adawi N. Endometrial scratching to improve pregnancy rate in couples with unexplained subfertility: a randomized controlled trialJ Obstet Gynaecol Res. 2013;39(3):680-684. doi:10.1111/j.1447-0756.2012.02016.x
  24. Vitagliano A, Noventa M, Saccone G, et al. Endometrial scratch injury before intrauterine insemination: is it time to re-evaluate its value? Evidence from a systematic review and meta-analysis of randomized controlled trialsFertil Steril. 2018;109(1):84-96.e4. doi:10.1016/j.fertnstert.2017.09.021
  25. Lensen S, Osavlyuk D, Armstrong S, et al. A Randomized Trial of Endometrial Scratching before In Vitro Fertilization. N Engl J Med. 2019;380(4):325-334. doi:10.1056/NEJMoa1808737
  26. Vitagliano A, Di Spiezio Sardo A, Saccone G, et al. Endometrial scratch injury for women with one or more previous failed embryo transfers: a systematic review and meta-analysis of randomized controlled trialsFertil Steril. 2018;110(4):687-702.e2. doi:10.1016/j.fertnstert.2018.04.040
  27. Check JH, Check ML.  A case report demonstrating that follicle maturing drugs may create an adverse uterine environment even when not used for controlled ovarian hyperstimulation.  Clin Exp Obst Gyn 28:217-218, 2001.

 

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