Verhoogt ‘scratching’ van het baarmoederslijmvlies de kans op een spontane zwangerschap in paren met onverklaarde verminderde vruchtbaarheid en een spontane kans op zwangerschap van >30%?

Hypothesis: In up to 50% of subfertile couples infertility is diagnosed as being ‘unexplained’. Some of these couples may have an endometrial factor that negatively impacts implantation. It has been suggested that the chances of implantation after IVF are increased by intentionally injuring (‘scratching’) the superficial lining of the womb. The inflammatory response will enable the endometrium to acquire a state of optimal receptivity thereby positively affecting live birth rates. Women with unexplained infertility following expectant management may also benefit from this scratching procedure.

Research question: Does endometrial scratching increase live birth rates in couples with unexplained infertility and a good prognosis (Hunault>30%)?

Study design: Randomized controlled non-blinded multi-center superiority trial with 12 months of follow-up

Study population Subfertile women who have completed their subfertility work-up and have a prognosis according to Hunault of > 30%.

Intervention: Endometrial scratch 6/7 days after the LH-surge

Comparison: No endometrial scratch

Main study outcomes: Cumulative live birth rate, Clinical pregnancy rate, Costs

Sample Size: Based on previous studies we expect the 12 month LBR to increase by 10% (35% in controls to 45% in scratch). To prove this superiority we will have to include 377 women in each arm to be able to detect this difference with a power of 80% (two-sided alpha 0.05). Anticipating 5% loss to follow up we need to include 792 women.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients who are randomized for endometrial scratching will pay one extra visit to the hospital. From existing literature it is clear that the rate and extent of adverse events is very low. The benefit is a potential increase in the chance to conceive for patients following expectant management.

In up to 50% of subfertile couples infertility is diagnosed as being ‘unexplained’. Some of these couples may have an endometrial factor that negatively impacts implantation. It has been suggested that the chances of implantation after IVF are increased by intentionally injuring (‘scratching’) the superficial lining of the womb. The inflammatory response will enable the endometrium to acquire a state of optimal receptivity thereby positively affecting live birth rates. Women with unexplained infertility following expectant management may also benefit from this scratching procedure.

12 months of FU

The scratch will be performed in a natural cycle with LH testing. The scratch will be performed 6 to 7 days after the positive LH test. If, for the individual patient, scheduling on this day is impossible then a scratch on day positive LH +5 or +8 is also okay. Women will receive instructions that they need to make sure that they are not pregnant in the scratch cycle (no sexual intercourse or sexual intercourse with appropriate contraceptive methods (e.g. oral contraception or condoms)). On the day of the scratch the gynecologist will verify if the woman has followed these instructions and only then will he/she start the procedure. The endometrial scratch will be performed by a maximum of 2 to 3 experienced and dedicated gynecologists per center. After exposing the uterine cervix and extensive cleaning with sterile water, the endometrial biopsy catheter will be gently introduced through the cervix up to the uterine fundus. The piston will then be drawn back to the end of the biopsy cannula, creating a negative pressure. To cover the entire endometrium, the examiner will apply a slow retraction of the device, while rotating the endometrial biopsy catheter over several ranges of 360 degrees. The procedure will be performed during 1-2 minutes. The obtained tissue will be snap-frozen in liquid nitrogen and transferred into a minimum of 3 FluidX tissue sample storage tubes (productnumber 68-4000) and stored at -80 degrees Celcius for later analysis. Each sample storage tube should be labelled with a unique label (which will be provided by the UMC Utrecht). A minimum block of 4mm tissue per tube should be stored.