This letter to the editor addresses points that were clearly stated in the article. Here are the responses point-by-point to this letter:

(I) The purpose of this randomized controlled trial (RCT) was to compare 2 completely different in vitro fertilization (IVF) protocols. The article never stated that the study was a “blinded” randomized trial: how can one randomize 2 different IVF protocols blindly:

• a)
  

  When one arm had fresh embryo transfer while the other had frozen embryo transfer?

  
  
• b)
  

  When one arm had oral medications (eg, clomiphene citrate) while the other arm did not?

  
  
• c)
  

  When one arm clearly had ONE embryo transferred while the other arm had TWO embryos transferred?

  
  
• d)
  

  When one arm had oocyte maturation trigger with nasal medication while the other arm had intramuscular medication?

Additionally, the following was stated in the “Methods” section: “Women and medical staff were not blinded for treatment allocation.”

Most importantly, this study was started in February 2009 (as stated in the “Methods” section). This is years before the American Society for Reproductive Medicine (ASRM) published their guidelines: “Criteria for embryo to transfer: a committee opinion” in 2013 when a single embryo transfer (SET) for younger women was recommended. Thus, we do not see any breach for the ASRM guidelines, especially because we have since implemented SET for all our patients.

(II) We disagree with the authors of this letter because, as stated in the “Methods” section, “The randomization was done at the start of the cycle using sequentially numbered opaque envelopes that had been prepared on the basis of a computer-generated list at the Academic Medical Center in the Netherlands and sent to NHFC [New Hope Fertility Center] in New York.” How else can randomization of participants for 2 different IVF protocols be performed?

The authors of this letter missed the following: “Secondary outcomes were clinical pregnancy rate, ovarian hyperstimulation syndrome, multiple pregnancy rate…” and “There are several limitations to our study: First and foremost, we compared two completely different strategies thus preventing us to disentangle the effects of various components of mini-IVF such as SET….” It was stated clearly that the difference in multiple pregnancy rates between both arms was due to the difference in the number of embryos transferred in each arm.

(III) Rejecting a primary hypothesis is not a “failure” as claimed by the authors of this letter. The conclusion in the abstract and the article clearly stated that mini-IVF is inferior to conventional IVF: “Compared to conventional IVF with double embryo transfer, mini-IVF with single embryo transfer lowers live birth rate….”

(IV) Although 120 out of 279 patients had fresh embryo transfers, there were 235 embryos transferred in these 279 patients over a 6-month period. As seen in Table 4, 214 (111+67+25+9+2) frozen embryos were transferred in the conventional IVF arm. The live birth rates in the conventional IVF arm ranged, clearly not artificially inflated, from 33-62% per cycle (see Table 4). There was no banking of embryos in the conventional IVF arm, as claimed, since each participant had 2 embryos (when available) and had cryopreservation of the surplus embryos. Patients who did not have any embryo transfer because of the failure to produce any embryos were accounted for and were included in the denominator of the statistics.

(V) It is not clear what this comment means since our study agreed with what they are claiming. Our RCT clearly showed that mini-IVF is inferior to conventional IVF. Additionally, it is a clear fact that patients with a poor prognosis, who were excluded in our RCT, will have worse outcome with conventional stimulation and minimal stimulation IVF.