Endometrial Biopsy Helps Unexplained Infertility

Endometrial Biopsy Helps Unexplained Infertility
For women with unexplained infertility, implantation failure may be common; over 50% of embryos are thought not to implant successfully. Everything may look good cycle after cycle: good lining, good follicle, good blood work but pregnancy simply doens't happen.

If this situation sounds familiar you may want to explore the merits of endometrial biopsy; superficial scratches to the uterus surface may change the immunological environment favorably and increase the likelihood of a successful conception and pregnancy. This technique - called endometrial scratching or endometrial biopsy - has been found to help women with unexplained infertility to conceive.

An Egyptian study (1) - published in the Journal Obstetrics And Gynaecology Research, 2012 - was one of the first to examine the effect of a single uterine scratching procedure in women with unexplained infertility. A group of 105 couples who had experienced unexplained infertility for over a year were randomized to undergo a four quadrant endometrial scratch procedure in the luteal phase of a natural menstrual cycle - or no scratching - and conceptions were tracked for the following 6 months.

For women who underwent endometrial scratching, the clinical pregnancy rate was more than double that of the control group: 25.9% versus 9.8% over a six month period and miscarriage rates were similar though marginally lower in the endometrial scratching group: 12.5% versus 16.5%. The study concluded that:

"Endometrial scratching may improve clinical pregnancy rates in couples with unexplained infertility. Adequately powered studies are mandated to confirm or refute the findings."

In this study, the biopsy was performed in the luteal phase between days 21 and 26 and the procedure was followed by a 5 day course of the antibiotic doxycycline, orally, 100 mg twice a day to prevent infection.

In a further study on the effectiveness of endometrial biopsy for couples with unexplained sub-fertility attempting non-IVF conception cycles, similarly positive results were obtained. In this study (2) which was a randomized clinical trial, conducted in Shiraz University Infertility Clinic of Ghadir Hospital 217 women with unexplained infertility aged 23-35 years old were divided into two groups and studied.

After taking clomiphene citrate and gonadotropins to induce ovulation the women were the women were randomized to receive endometrial scratch biopsy - on the back wall of the uterus - when a dominant follicle reached maturity at 18-20 mm. The procedure was performed prior to ovulation and results demonstrated that conception rates more than doubled in women who underwent biopsy (14.9% versus 5.8%). The study concluded:

"Local mechanical injury of the endometrium can enhance the uterine receptivity and facilitates the embryo implantation."

"This simple, easy, and cost effective procedure is worth considering in selective unexplained infertility patients who implantation failure is the likely causes of infertility before complex treatments."

"This procedure may help reduce psychological tensions and high expenses imposed through such interventions."

Although these are the first studies on endometrial scratching for the treatment of unexplained fertility, a number of studies have evaluated the value of this technique for women undergoing IVF when there has been a history of implantation failure. Logically one would expect to see similar results from using the procedure for treating implantation failure in unexplained infertility.

In my practice, women undergoing IVF who have undergone this technique have often had successful pregnancies after long-term implantation failure. Here are some conclusions from prior studies on endometrial scratching and IVF.

A huge 2012 review (3) from the University of Liverpool, UK, published in Reproductive Medicine Online examined the effectiveness of endometrial injury for recurrent implantation failure in women undergoing IVF. The review pooled data from seven controlled studies (four randomized and three non-randomized), with 2062 participants and concluded that:

"...local endometrial injury induced in the cycle preceding ovarian stimulation is 70% more likely to result in a clinical pregnancy as opposed to no intervention...."

"The evidence is strongly in favour of inducing local endometrial injury in the preceding cycle of ovarian stimulation to improve pregnancy outcomes in women with unexplained RIF (recurrent implantation failure)."

"The results suggest that inducing injury is 70% more likely to result in a clinical pregnancy as opposed to no treatment."

"Furthermore, scratching of the lining was 2-times more likely to result in a clinical pregnancy compared with telescopic evaluation of the lining of the womb."

"This study suggests that in women with RIF, inducing local injury to the womb lining in the cycle prior to starting ovarian stimulation for IVF can improve pregnancy outcomes."

Another 2012 review (4) of randomized control trials on this technique by the Cochrane database included 591 women and also concluded favorably that endometrial scratching makes the uterus more baby-friendly and more likely to secure implantation:

"Endometrial injury performed prior to the embryo transfer cycle improves clinical pregnancy and live birth rates in women undergoing ART..."

Mor recently, a 2016 study (5) on women with unexplaine infertility undergoing IUI after treatment with Clomid also found that pregnancy rtes increased after endometrial scratching.

One hundred and fifty four infertile women received 100 mg of oral clomiphene citrate for 5 days starting on day 3 of the menstrual cycle. Patients were randomized to 2 equal groups: Group C received IUI without ESI and group S had ESI. Successful pregnancy was confirmed by ultrasound.

The pregnancy rate (cumulative) over 3 cycles of treatment was 39% in women who underwnt endometrial scrtching compared with just 18.2% in women who were treated with Clomid alone.

"The ESI significantly improves the outcome of IUI in women with unexplained infertility especially when conducted 1 month prior to IUI."

Although more studies are needed top IVF clinics have been using endometrial scratching to improve pregnancy success for some years now and many progressive fertility physicians now allow women to pursue this treatment. The procedure is simple and quick and OB/GYNs are usually very familiar with this technique which is used for performing standard uterine biopsies.

If you do undergo this in-office procedure it can be a little ouchy, be sure to ask your physician about ways to minimize any discomfort with anti-inflammatory medication or a topical such as 'Emla'.
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Please note: This article is not intended to diagnose or to provide medical or dietetic treatment for which you should see a physician or dietitian. You are encouraged to discuss any new treatments or diet changes that you wish to pursue with your physician.

(1) J obstet Gynaecol Res. 2012 Oct 29. doi: 10.1111/j.1447-0756.2012.02016.x. [Epub ahead of print]
Endometrial scratching to improve pregnancy rate in couples with unexplained subfertility: A randomized controlled trial.
Gibreel A, Badawy A, El-Refai W, El-Adawi N.

(2) Iran J Reprod Med. 2013 Nov;11(11):869-74.
Pregnancy rate after endometrial injury in couples with unexplained infertility: A randomized clinical trial.
Parsanezhad ME1, Dadras N1, Maharlouei N2, Neghahban L1, Keramati P1, Amini M1.

(3) Reprod Biomed Online. 2012 Dec;25(6):561-71. doi: 10.1016/j.rbmo.2012.08.005. Epub 2012 Sep 12.
Endometrial injury to overcome recurrent embryo implantation failure: a systematic review and meta-analysis.
Potdar N, Gelbaya T, Nardo LG.

(4) Cochrane Database Syst Rev. 2012 Jul 11;7:CD009517. doi: 10.1002/14651858.CD009517.pub2.
Endometrial injury in women undergoing assisted reproductive techniques.
Nastri CO, Gibreel A, Raine-Fenning N, Maheshwari A, Ferriani RA, Bhattacharya S, Martins WP.

(5) Reprod Sci. 2016 Feb;23(2):239-43. doi: 10.1177/1933719115602776. Epub 2015 Sep 3.
Endometrial Scratch Injury Induces Higher Pregnancy Rate for Women With Unexplained Infertility Undergoing IUI With Ovarian Stimulation: A Randomized Controlled Trial. Maged AM1, Al-Inany H2, Salama KM3, Souidan II3, Abo Ragab HM3, Elnassery N2.




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