ESHRE: Limited Evidence for Novel Conception Aids

— Mixed results for endometrial scratching, immobilization, and HGH

MedicalToday

HELSINKI -- Several studies presented here examined novel or controversial methods of boosting conception rates for assisted reproductive technologies and spontaneous conception -- with varying results.

Endometrial "scratching" is described as slightly controversial. It is "a cheap and simple procedure" where the lining to the womb is purposely irritated by pipelle biopsy or similar device without analgesia during a clinic visit. Performing this procedure prior to either intrauterine insemination or spontaneous conception was associated with a more than two-fold increase in the probability of live birth or an ongoing pregnancy (RR 2.26, 95% CI 1.54-3.32), a meta-analysis suggested.

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

This means that endometrial scratching would increase the chance of a pregnancy or live birth from 9% without intervention to somewhere between 14% and 28%, reported , of University of Auckland in New Zealand, and colleagues.

There was also an almost two-fold increase the probability of clinical pregnancy (RR 1.92, 95% CI 1.44-2.55) when the method was compared with either no scratching or "mock" scratching.

"The leading theory on the effectiveness of endometrial scratching is the action of causing a scratch to the lining of the womb produces a small inflammatory response, just as if you'd scratched your arm," said Lensen in an interview. "The thought is the biological receptors released as part of the inflammatory response also signal the embryo to implant in the lining of the womb, and therefore cause an increased chance of getting pregnant."

This technique has been previously had success in patients undergoing IVF, but has not yet been proven in patients undergoing IUI or attempting spontaneous conception. So, Lensen's team performed a Cochrane review of the eight randomized trials that focused on endometrial scratching and these two conception methods.

They presented their results at the annual meeting, but warned that most of the randomized trials had a serious risk of bias and the results should be treated with caution.

There was no evidence that endometrial scratching increased the risk of miscarriage, ectopic pregnancy, or multiple pregnancies, the researchers noted.

Immobilizing Patients After IUI Has No Impact on Pregnancy Rates

A single-center randomized controlled trial found that there was no significant difference in pregnancy rates following intrauterine insemination (IUI) when the patient was put on bed rest for 15 minutes following the procedure compared with being allowed to immediately move around.

Two recent studies -- and "widely held beliefs" -- have indicated that there may be a benefit to keeping patients immobilized, but , of VU University Medical Center in Amsterdam, and colleagues, found pregnancy rates were actually higher when the patient was allowed to move around (40.2% following immediate mobilization versus 32.2% following 15 minutes of bed rest).

"We believe our results ... are solid, and sufficiently strong to render the recommendation for bed rest obsolete," van Rijswijk said in a statement.

The higher pregnancy rates with immediate mobilization actually came close to statistical significance (P=0.065). After adjusting for duration of subfertility, the results remained similar (adjusted OR for pregnancy with rest versus immediate mobilization 0.72, 95% CI 0.491-1.044, P=0.082).

Researchers examined 236 participants who were assigned to 15 minutes of immobilization and 243 patients who were allowed to be immediately mobile following the procedure. Patient characteristics were similar, though the immobilization group had a longer duration of subfertility (2.4 years versus 2.1 years, respectively).

Van Rijswijk characterized the benefits historically associated with immobilization following IUI as "coincidence," adding that the authors of the earlier studies had no explanation for why pregnancy rates were better if the patient had a short period of bed rest.

"There is still a chance the difference is based on coincidence or caused by IUI cycles or maybe there's another biological mechanism which we don't know," she said in an interview. "We are planning to do a meta-analysis to see if there is still a difference and I don't think there will be."

HGH Flops as Pregnancy Aid

Recombinant human growth hormone (rHGH) is used in women who are poor responders to IVF, but a small study found no significant difference in pregnancy rates between patients who used rHGH and patients who used a placebo.

In an intention-to-treat analysis, the pregnancy rate for the rHGH group was 14%, while the pregnancy rate for the placebo group was 11%, reported , of University of Adelaide and FertilitySA in Australia, and colleagues.

"There are almost no randomized controlled studies where either placebo or growth hormone are given, and outcomes look at live birth instead of the number of eggs or the number of embryos," said Norman in an interview. "We were unable to prove any benefit for growth hormone either in pregnancy rate or the live birth rate."

There were also no significant differences between the two groups in terms of the number of eggs collected, the quality of embryos, and the duration of treatment in the current work.

The study had originally planned to examine 390 women who had a previous IVF cycle with no more than five eggs collected after maximum stimulation, as well as ovarian stimulation with the same drug dose. Ultimately, 116 patients were enrolled in the trial: 66 to rHGH and 65 to placebo. There were 25 total pregnancies and 16 total live births, including three sets of twins in the rHGH group.

Four serious adverse events (congenital anomalies) occurred: three in the rHGH group and one in the placebo group.

The authors noted that the study was actually terminated after 4 years due to slow recruitment (mainly due to patients buying their own growth hormone) and the original number for enrollment was not reached, so the study was underpowered to answer the question definitively.

Disclosures

Lensen and colleagues disclosed no relevant financial relationships.

Van Rijswijk and colleagues were partially supported by the VU University Medical Center in Amsterdam, The Netherlands.

Norman and colleagues were partially supported by Merck Serono, which provided a small amount of the total funding.

Primary Source

European Society of Human Reproduction and Embryology

Lensen S, et al "Endometrial scratching for pregnancy following sexual intercourse or intrauterine insemination (IUI): a Cochrane systematic review and meta-analysis" ESHRE 2016; Abstract P-287.

Secondary Source

European Society of Human Reproduction and Embryology

Van Rijswijk J, et al "Should patients be immobilised after intrauterine insemination? A randomised controlled comparison between 15 minutes of immobilisation and direct mobilisation" ESHRE 2016; Abstract O-165.

Additional Source

European Society of Human Reproduction and Embryology

Norman RJ, et al "A randomised double blind placebo controlled study of recombinant human growth hormone (r-HGH) on live birth rates in women who are poor responders" ESHRE 2016; Abstract O-082.