Human Reproduction, Vol. 17, No. 7, 1927,
July 2002
© 2002 European Society of Human Reproduction and Embryology
Different aetiological mechanisms for unexplained and endometriosis-associated infertility cannot be inferred from unstimulated IVF cycles using HCG to induce ovulation
3 Department of Obstetrics and Gynecology, National Hospital, Geir Aamodt, Department of Biostatistics, National Hospital, University of Oslo, Norway
| Introduction |
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Dear Sir,
We appreciate the interest of Dr Keay and Dr Cahill in our paper (Omland et al., 2001
). Their comment emphasizes the difficulties in comparing results in different study set-ups. We realize, as also pointed out in the paper, that by using HCG for ovulation induction the luteal phase would be influenced, and hormonal values thereafter could only serve as a comparison of this response in the studied infertility groups. We also realized that by using HCG the denomination completely natural cycle IVF would be imprecise. We agree that the denomination natural cycle IVF perhaps should be reserved for the cases completely free of exogenous medication, but to our knowledge this strict definition is not officially agreed upon. We applied the same method as described by Paulson et al. in 1992 (Paulson et al., 1992
) and also used by Daya and referred to by Janssens among others. (Daya et al., 1995
; Janssens et al., 2000
). The expression Natural cycle IVF was used in combination with GnRH antagonist in the publication by Rongières-Bertrand in 1999 (Rongières-Bertrand et al., 1999
) and we agree with Dr Keay and Dr Cahill that unstimulated cycle in combination with GnRH antagonist would be more precise.
We are of course familiar with the inspiring research by Cahill and colleagues. The logistics of their paper from 1995 (Cahill et al., 1995
) with serum samples every 4 hours from follicle diameter >14mm until oocyte recovery, were, alas, an impossibility for our group. Our serum samples were obtained between 0800 h and 0900 h from cycle day 3 to 27. Samples for FSH, LH and estradiol were collected every other day except from cycle day 9 to 17, where estradiol and LH were obtained daily. FSH samples were obtained every other day throughout the cycle as were progesterone from cycle day 9.
The fact that HCG was used after fixed arbitrary criteria, as stated in our paper, would explain the relevant differences between Cahill and colleague's paper and ours.
We see no conflict in Keay and Cahill's statement that their determination of follicular phase length, AUC, LH and peak LH measurements more correctly reflect the natural physiological conditions as ours are influenced by the timing of HCG injection and its use. However, our results could reflect a response to HCG in the studied groups that over-ride these differences.
We also appreciate the comments on our statistical results. We regret that some of the data were presented in a way that could confuse the reader as to the choice of method used. We calculated, by means of SPSS, for each patient, the number of fertilized oocytes, the pregnancy rate (PR)/initiated cycle, the PR/successful oocyte retrieval and the PR/embryo transfer (Table I
). These continuous data were not assumed to be normally distributed. The median, maximum and minimum values for each diagnostic group were left out, causing Keay and Cahill to assume the use of
2, whilst MannWhitney was applied. The statistical analyses were approved by the hospital's Department of Biostatistics. The data given in Table I
should clarify these points.
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The ascribed cleavage rates by Keay and Cahill of 62.2 and 68% of two of our infertility groups were incorrect. Both the unexplained and the tubal factor groups had a cleavage rate of 100%, whereas the endometriosis-associated group had a cleavage rate of 85% (34/40).
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1 To whom correspondence should be addressed. E-mail: anne.omland{at}r\|[iacute]\|kshospitalet.no
| References |
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Daya, S., Gunby, J., Hughes, E.G., Collins, J.A., Sagle, A. and Young Lai, E.V. (1995) Natural cycles for in-vitro fertilization: cost-effectiveness analysis and factors influencing outcome. Hum. Reprod., 10, 17191724.
Cahill, D.J., Wardle, P.G, Maile, L.A., Harlow, C.R and Hull, M.G.R. (1995) Pituitary-ovarian dysfunction as a cause for endometriosis-associated and unexplained infertility. Hum. Reprod., 10, 31423146.
Janssens, R.M.J., Lambalk, C.B., Vermeiden, J.P.W., Schats, R., Schoemaker, J. (2000) In-vitro fertilization in a spontaneous cycle: easy, cheap and realistic. Hum. Reprod., 15, 314318.
Omland, A.K., Fedorcsak, P., Storeng, R., Dale, P.O., Åbyholm, T., Tanbo, T. (2001) Natural cycle IVF in unexplained, endometriosis-associated and tubal factor infertility. Hum. Reprod., 16, 25872592.
Paulson, R.J., Sauer, M.V., Frances, M.M., Macaso, T.M, Lobo, R.A. (1992) In vitro fertilization in unstimulated cycles: the University of Southern California experience. Fertil. Steril., 57, 290293.[ISI][Medline]
Rongières-Bertrand, C., Oliviennes, F., Righini, C., Fanchin, R., Taïeb, J., Hamamah, S., Bouchard, P., Frydman, R. (1999) Revival of the natural cycles in in-vitro fertilization with the use of a new gonadotrophin-releasing hormone antagonist /Cetrorelix): a pilot study with minimal stimulation. Hum. Reprod., 14, 683688.
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