Consumer-friendly reporting of in vitro fertilization outcomes

29 10 2013

To the Editor:

Dr. David Meldrum proposes a revision of the clinic-specific Society for Assisted Reproductive Technology (SART)/Centers for Disease Control and Prevention (CDC) reporting format to better reflect the current practice of in vitro fertilization (IVF) by combining the outcomes of fresh and frozen embryo transfers in the numerator while making transfer procedure the denominator of choice (1). I concur with the first but disagree with the second part of his proposal, making transfer the preferred denominator without regard to the number of retrievals contributing embryos to the transfer. In addition to accuracy, a reporting system needs to be readily accessible to potential consumers.

With accumulation of eggs from multiple retrievals for a single transfer, this metric fails to differentiate between two distinct scenarios: A) one live birth from one transfer and one retrieval; B) one birth from one transfer following, say, four retrievals (2). Both scenarios generate 100% delivery rate per transfer, but the delivery rate per retrieval is 100% for scenario A but only 25% for scenario B. Such a reporting system would be misleading and leave patients vulnerable to exploitation by volume-driven clinics.

In the case of high responders, a single retrieval may lead to more than one live birth from sequential frozen embryo transfers (FETs), thus elevating the delivery rate per retrieval above 100% unless all births after the first one are censored—a crucial point the author does not address. Read the rest of this entry »

Comment on “Progesterone elevation does not compromise pregnancy rates in high responders: a pooled analysis of in vitro fertilization patients treated with recombinant follicle-stimulating hormone/releasing hormone antagonist in six trials”

24 10 2013

To the Editor:

I read with great interest and attention the original article published recently by Griesinger et al. (1) entitled “Progesterone elevation does not compromise pregnancy rates in high responders: a pooled analysis of in vitro fertilization patients treated with recombinant follicle-stimulating hormone/releasing hormone antagonist in six trials.” In this article, Griesinger et al. conclude that a progesterone (P) elevation > 1.5 ng/mL on the day of hCG administration is associated with a lower ongoing pregnancy rate (OPR) in the general population, but not in patients with a high ovarian response, defined as an oocyte yield > 18 oocytes.

These authors performed excellent statistical work, pooling data from six multicenter randomized controlled trials relatively similar in their design, and presented the results as if all came from one single study. However, the study deserves several comments that question the unequivocal conclusion that is presented even in the title of the manuscript. Read the rest of this entry »

Haplotypes and polymorphisms of the ANXA5 nontranslated region in Japanese and European women with recurrent miscarriage and in controls

9 10 2013

To the Editor:

Yuko Hayashi and coauthors confirm single nucleotide polymorphism (SNP) rs1050606 (SNP5) of the nontranslated region of the ANXA5 gene as a risk factor for recurrent miscarriage (RM) in Japanese patients (1). They also conclude that the risk allele has no influence on pregnancy outcome from 79 abortions that occurred from November 2012 to February 2013 in a group of 264 Japanese women with RM history in Nagoya City University Hospital. Almost two-thirds of the 79 aborted fetuses, or ~ 64% had abnormal karyotypes, which leaves only n = 17 cases possibly influenced by thrombophilia through carriage of common ANXA5 SNPs/haplotypes, among other factors. Moreover, since no data about the timing of miscarriages are shared, but the majority of abortions in the patient group are apparently due to chromosomal aberrations, it is rather likely this is an early (predominantly before 10th week of gestation) RM group. It is certainly very plausible that live birth rates in such a preselected cohort would not be notably influenced by carriage of ANXA5 SNPs/haplotypes, as M2/ANXA5 for example should not be significant as a risk factor before weeks 10 to 12 of gestation (2). Read the rest of this entry »

Focus on the importance of soluble HLA-G as a marker for embryo selection in ART

8 10 2013

To the Editor:

We have read with interest the paper by Kotze et al. (1), reporting the retrospective analysis of 2,040 patients for the expression of soluble HLA-G (sHLA-G) by day-2 embryos after intracytoplasmic injection. The data represent further confirmation of the role of sHLA-G molecule quantification in embryo culture supernatants as a marker for embryo selection (2). In pregnancy several tolerance mechanisms have been demonstrated to counteract the maternal immune response. Among these, the expression of HLA-G by invasive cytotrophoblasts has been shown to play a fundamental role in creating a tolerogenic condition at the feto-maternal interface (2).

By now, more than 15,000 embryo culture supernatants have been evaluated for sHLA-G expression, with a positive correlation with embryo implantation rate and pregnancy outcome. However, further research is needed in HLA-G investigation in assisted reproductive technology (ART). Three aspects should be taken into consideration: 1) recognition of a common sHLA-G detection protocol; 2) necessity to identify a standardized range for positivity, as reported by Kotze et al. (1); 3) comprehension of the factors involved in the differential expression of sHLA-G between equal stage embryos originating from the same woman (3). Read the rest of this entry »