Non-surgical dilation for vaginal agenesis is promising, but better research is needed

To the Editor:

We write with concerns about the paper “Mayer-Rokitansky-Küster-Hauser syndrome: a review of 245 consecutive cases managed by a multidisciplinary approach with vaginal dilators” (1). Whilst we agree with the authors that non-surgical dilation supported by a multi-disciplinary team is a promising approach, we also wish to highlight the deficiencies in this report.

The methods section consists of a description of the dilation programme with no research methodology in what is positioned as an intervention study. There is no mention of ethical approval or consent. Referral and attendance at a clinical service per se cannot be construed as informed consent to be researched. There is no description of how patients were recruited for the study or how women were assessed for treatment completion – whether at clinic, by telephone, or postal questionnaires. The abstract states functional vaginal length as one of the main outcome measures, whilst the results refer to anatomical vaginal length. These are different assessments, depending on whether an individual is sexually active. The authors refer to “clinical examination” but do not describe what this entailed, and although they defined success as a vaginal length of more than 6 cm, there was no description of how this was derived.

Elimination of OHSS

To the Editor:

I read with interest the recently published discussion on the etiology and prevention of OHSS (1-2). While the reviews comprehensively covered their aims, there are some issues that should be highlighted.

Agonist and antagonist coast

Coasting, or the complete discontinuation of exogenous gonadotropin while continuing GnRH analogues administration, is a preventive measure that is completely related on serum E2 levels at gonadotropin discontinuation and on the drop in E2 levels on day of hCG administration (1). However, while “it is well established that high E2 levels are associated with a high incidence of OHSS” (1), OHSS may occur in patients who conceived spontaneously, and in those with low or high serum E2 levels on the day of hCG administration (details in ref. 3). These versatile observations actually suggest that the previously accepted risk factors to develop OHSS, especially high serum E2 levels, are unreliable for the prediction of severe OHSS (3).

Therefore, we were not surprised at the finding of the recently published Cochrane review (4), which reported no difference in the incidence of moderate or severe OHSS after coasting.

Etiology of OHSS

To the Editor:

I read with interest the recently published discussion on the etiology and prevention of OHSS (1). While the review comprehensively covered its aims, there are some issues that should be highlighted.

OHSS, being a major complication of controlled ovarian hyperstimulation (COH), is characterized by marked ovarian enlargement and acute third space fluid sequestration that almost always develops after hCG administration or in early pregnancy. OHSS is similar to vascular leak syndrome (VLS), which may be attributable to the massive increase in systemic inflammatory cytokines, including vascular endothelial growth factor (VEGF), observed also during the course of severe OHSS (2).

As was already mentioned (1), many factors and mediators have been proposed as the intermediate, released by gonadotropin-hyperstimulated ovaries at ovulation, which causes the increase in capillary permeability. However, no significant evidence exists to prove any absolute or ultimate role of these ovarian regulators in the pathophysiology of OHSS (2).

Vitrification Carriers and European Regulation

To the Editor:

We read with interest the recent article by Valbuena et al. (1) comparing the efficiency of Cryotip vs. Cryotop for blastomere vitrification. The authors concluded that it is preferable to preserve individual human blastomeres using Cryotip, which is a closed system. Furthermore, they suggest that this has the advantage of complying with European Union directives.

We would like to point out that European Union directives on tissue manipulation (European Union Tissues and Cells Directive EUTCD: 2004/23/EC, 2006/17/EC and 2006/86/EC) have been issued by the European Parliament in order to increase the safety and quality of tissues – including reproductive cells – processed for human re-implantation through the control of equipment, devices and environment. These regulations require specific procedures in embryo/oocyte/ovarian tissue cryopreservation in order to minimize the risk of any hypothetical contamination of human cells due to direct contact with accidentally contaminated liquid nitrogen (LN2).