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The field of assisted reproductive technology is shaped and changed constantly by advances in science and cutting-edge innovations. In a quest to maximise outcomes, add-on interventions are often adopted and utilised prematurely while the principles of evidence-based medicine seem to be less strictly adhered to. In this review we will attempt to summarise the latest evidence about some of the adjuvants.

Objectives To test the hypothesise that the treatment protocol used for preparation of the endometrium for frozen embryo transfer (ET) has a beneficial effect on the disorganised endometrium in women with endometriosis and leads to a higher pregnancy rate. Study design We performed a retrospective, database-searched cohort study. Relevant information was collected from the electronic records of women who underwent IVF/ICSI between 1/1/2000 and 31/12/2008 in our unit. Endometriosis patients formed the study group. The rest of the women formed the control group. The two groups were subdivided, depending on whether they had fresh or frozen ET. The main outcome was live birth rate (LBR). Secondary outcomes were clinical pregnancy rate (CPR) and miscarriage rate (MR). Comparisons were performed by Chi-square and Mann–Whitney tests (SPSS 16.0). Results A total of 3763 fresh and 3523 frozen ET IVF cycles were included in our study, of which 415 (5.7%) were due to endometriosis related subfertility. In the non-endometriosis group, fresh ET had significantly higher LBR, CBR and MR than frozen ET. In women with endometriosis, down-regulated frozen ET cycles had a markedly high LBR and CPR (16.9%, 18.2%), comparable to the LBR and CPR of fresh ET cycles in the same group (19.5%, 20.2%). No significant differences were found in the LBR and CPR in fresh ET cycles between the study and the control group. In frozen ET, however, the CPR was significantly higher in the endometriosis group (18.2% versus 12.7%, P =0.048). Conclusion Unlike the general IVF population, in women with endometriosis undergoing IVF, the preparation of the endometrium for frozen ET with GnRH agonists compared to fresh cycles is associated with higher LBR (16.9% versus 11.9%) and a significantly higher CPR (18.2% versus 12.7%, P =0.048). These results suggest that, in cases of endometriosis, the combined effect of GnRHa on the endometrium and the low level of ovarian steroids may simultaneously offer a better endometrial environment for implantation which may lead to better outcomes.

The loss of three or more consecutive pregnancies, known as recurrent miscarriage (RM), affects approximately 1 % of couples. Aetiology can be varied but in up to 50 % of the cases the cause remains unexplained. Progestogen supplementation has been used for more than half a century for the treatment of recurrent miscarriage in different doses and routes of administration. Progesterone activity is mediated via specific progesterone receptors, and is considered crucial for the development of an endometrial environment suitable for implantation. Progesterone regulates endometrial receptivity, and induces uterine quiescence. In addition, the immunomodulatory properties of progesterone, controlled by progesterone induced blocking factor (PIBF), seem to be also important for the maintenance of early pregnancy. In women with RM there may be a degree of immunological intolerance, progesterone may benefit these women by altering the immune response to the embryo. Despite favourable meta-analyses on the use of progestogens in RM, the evidence is not considered to be solid and data from ongoing research are awaited.

There are inherent difficulties in defining infertility and unexplained infertility (UI), and the scientific community is yet to reach a consensus opinion. These difficulties stem from the differences in the clinical, epidemiological and demographic approach in defining infertility.