More than 50% of colleagues worldwide are not flushing follicles during egg collection.  The primary reason for this are studies, published in the early nineties, comparing egg retrievals using two needles with the same outer diameter (Single Lumen Needles and Double Lumen Needles). All of the authors concluded that that they harvested the same number of oocytes with either needle, but the duration of egg collection procedure took 2 to 3 times longer using the double lumen needles. 

A receptive endometrium is a prerequisite for successful implantation. Although embryo culture conditions in IVF treatment are constantly being improved and selection of the best embryo for transfer is based on more accurate features, one of the major barriers in human fertility is the failure of the uterus to become receptive.

The mechanism by which endometrial biopsy gains its favorable effect on IVF pregnancy outcome was recently suggested by our studies showing that the biopsy induced an increase in the levels of different pro-inflammatory cytokines and in the abundance of specific immune cells in the endometrium. These pro-inflammatory cytokines were previously detected in the endometrium during the window of implantation and are possibly involved in the recruitment of the immune cells to the tissue.  These immune cells secrete their own cytokines and growth factors that, in turn, induce cell proliferation and differentiation as well as vascularization. Most importantly, a positive correlation between the biopsy-induced pro-inflammatory cytokine and immune cell levels and pregnancy rate after IVF treatment was observed, clearly supporting our suggested mechanism.

Our initial protocol included 4 biopsies on days 8, 12, 21 and 26 of the spontaneous cycle preceding IVF treatment. A later study demonstrated a similar favorable effect by performing only two biopsies on days 21 and 26 of that cycle. Yet, a third study suggested that a single biopsy on day 5 of the treatment cycle is equally beneficial. In spite of this variance in the protocol, a recent meta-analysis of all of the above-mentioned studies shows the beneficial effect of the endometrial biopsy on IVF success rate. A large scale prospective randomized trial is now being conducted by us in order to establish the optimal protocol regarding the number and timing of the biopsy.

Many efforts are being invested in unraveling the complicated molecular mechanism of the development of a receptive endometrium. It was back in 1907 that scratching the uterus was first shown to induce decidualization in the guinea-pig. Later studies further demonstrated that formation of deciduas in rodents follows different kinds of trauma such as suturing the uterine horn and intrauterine oil  injection. This goes along with our intriguing findings first reported in 2003 that endometrial biopsies taken during the spontaneous menstrual cycle before IVF treatment substantially increased the implantation, clinical pregnancies and live birth rates. Our findings were later confirmed by other clinical centers worldwide that demonstrated an improvement in the success rate in IVF patients who had failed to conceive in several previous treatment cycles although good quality embryos were transferred into their uterus. Interestingly, different clinics use different biopsy protocols to gain the same positive effect on IVF outcome. 

Taken together, our findings suggest that inflammation is essential for the transition of the endometrium from a non-receptive to a receptive stage. This inflammatory process probably does not take place in IVF patients with recurrent implantation failure, necessitating the endometrial biopsy treatment.

This research is a fruitful collaboration between our IVF Unit headed by Dr. Amihai Barash, and Prof. Nava Dekel and Dr. Yulia Gnainsky from the Weizmann Institute of Science, Rehovot

 

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