City Hospital, Buklum Sokak 53, 06660 Kavaklidere, Ankara, Turkey
Dear Sir,
We have read with great interest the paper by Noci et al. (Noci et al., 1998), indicating that day 3 luteinizing hormone (LH) values <3 mIU/ml are predictive of poor response to ovarian stimulation in patients with normal basal follicle stimulating hormone (FSH) concentrations. In this study, no in-vitro fertilization (IVF) patients were included and patients treated by intrauterine insemination, direct intraperitoneal insemination and timed spontaneous intercourse were chosen as the study population (LH<3 mIU/ml, n = 30) or controls (LH>3 mIU/ml, n = 45). They found that the oestradiol peak and the number of follicles >15 mm diameter at the time of human chorionic gonadotrophin (HCG) administration were lower in the study group than in the control group and they concluded that in patients with normal basal FSH values, day 3 LH values <3 mIU/ml are predictive of poor response to ovarian stimulation. This study is in agreement with the study of Mukherjee et al. (1996) which recently reported that an elevated day 3 FSH:LH ratio in the presence of normal day 3 FSH is predictive of a poor response to ovarian stimulation and careful analysis of data suggested that the poor response could be due to low day 3 LH concentrations. The explanation of the negative impact of low LH concentration on cycle outcome may be related to the impaired balance between ovarian steroid concentration, peptide production, and pituitary secretion.
However, in the study of Noci et al. (Noci et al., 1998), the cycle cancellation rate was found to be 10.5% in patients with day 3 LH<3 mIU/ml and 6.7% in control patients and there was no statistically significant difference. They also did not give any other result indicating poor outcome, like pregnancy outcome etc. and just stated that the oestradial peak on the day of HCG administration and the number of follicles >15 mm in diameter were significantly lower in patients whose day 3 LH was <3 mIU/ml in a small patient population.
We previously showed the effectiveness of clomiphene citrate challenge tests in the prediction of poor outcome in patients undergoing intracytoplasmic sperm injection (ICSI) (Kahraman et al., 1997). We also evaluated the performance of day 3 LH values for predicting the cycle outcome in patients undergoing ICSI in a large group. According to our results, and in patients with normal FSH (<10 mIU/ml) and oestradiol (<50 pg/ml), the number of oocyte retrieval cycles and embryo transfers, the mean oestradiol value on the day of HCG administration, the number of retrieved oocytes, the number of metaphase II oocytes, the number of oocytes fertilized and the number of embryos were all significantly lower in patients with day 3 LH<3 (n = 196) than those patients with day 3 LH>3 (n = 268) (Table I
). Although there was no significant difference, the number of pregnancies and number of ongoing pregnancies per started cycle and per embryo transfer were also lower in patients with low day 3 LH concentrations (<3 mIU/ml). In our study, the predictive value of day 3 LH <3 mIU/ml was 54.4% for cycle cancellation and 45.9% for failing to conceive (Table II
).
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References
Kahraman, S., Vicdan, K., Isik, A.Z. et al. (1997) Clomiphene citrate challenge test in the assessment of ovarian reserve before controlled ovarian hyperstimulation for intracytoplasmic sperm injection. Eur. J. Obstet. Gynecol., 73, 177182.[ISI][Medline]
Mukherjee, T., Copperman, A.B., Lapinski, R. et al. (1996) An elevated day three follicle stimulating hormone: luteinizing hormone ration (FHS:LH) in the presence of a normal day 3 FHS predicts a poor response to controlled ovarian hyperstimulation. Fertil. Steril., 65, 588593.[ISI][Medline]
Noci, I., Biagiotti, R., Maggi, M. et al. (1998) Low day 3 luteinizing hormone values are predictive of reduced response to ovarian stimulation. Hum. Reprod., 13, 531534.[Abstract]
Department of Obstetrics and Gynaecology, University of Florence
Andrology Unit, Department of Clinical Physiopathology, University of Florence, 50134 Florence, Italy
Dear Sir,
We appreciate the interest shown by Vicdan and Isik in our report (Noci et al., 1998) indicating that the low day 3 luteinizing hormone (LH) values are predictive of reduced response to ovarian stimulation. The data they presented are indeed in apparent, perfect agreement with our results. These authors previously reported a positive predictive value of a clomiphene citrate challenge test in the assessment of ovarian reserve before ovarian stimulation for intracytoplasmic sperm injection (ICSI) performed for severe male infertility (Kahraman et al., 1997
). In this paper, the authors reported data on 198 women who underwent a challenge test before ICSI. They showed that in the 141 cases with normal test results, the outcomes of the subsequent ICSI cycle were better than in the 57 patients with abnormal test results. Although these results were interesting and sound we could not find, in this paper (Kahraman et al., 1997
), any mention of the predictive value of day 3 LH measurement. In the present Letter to the Editor, they extended their observation to 464 ICSI cycles, evaluating whether or not a low (<3 mIU/ml) day 3 LH value is predictive of a poor response to ovarian stimulation. They found a statistically significant difference in terms of cancelled cycles, oocyte retrieval cycles, fertilization failure, embryo transfers, gonadotrophin dose, oestradiol on the day of human chorionic gonadotrophin (HCG) administration, oocytes retrieved and fertilized, and number of embryos. As already mentioned, these results were apparently quite confirmatory of our data (Noci et al., 1998
). However, there is a main difference between our study and their study. Since all the observations of the Vicdan and Isik study have been obtained in patients undergoing an ICSI cycle, we assume that a down regulation protocol with gonadotrophin-releasing hormone (GnRH) analogue was employed. This is not the case in our study. In fact in our study all the women were not suppressed by a GnRH analogue. The assisted reproductive technology (ART) employed by us included intrauterine insemination, direct intraperitoneal insemination and timed spontaneous sexual intercourse cycles. Therefore while in our study LH from the pituitary is not suppressed and might affect follicular development, in their study LH is most probably suppressed and therefore less active at the ovarian level. This is because a prolonged treatment with GnRH analogues almost completely suppresses LH values (Noci et al., 1997
). Hence, we would like to stress that the two reports are indeed different. We are planning to extend the LH day 3 predictive value of ovarian responsiveness to GnRH analogue suppressed cycles.
We appreciate indeed the valuable comments by Drs Vicdan and Isik.
References
Kahraman, S., Vicdan, K., Isik, A.Z. et al. (1997) Clomiphene citrate challenge test in the assessment of ovarian reserve before controlled ovarian hyperstimulation for intracytoplasmic sperm injection. Eur. J. Obstet. Gynecol. Reprod. Biol., 73, 177182.[ISI][Medline]
Noci, I., Borri, P., Coccia, M.E. et al. (1997) Hormonal patterns, steroid receptors and morphological pictures of endometrium in hyperstimulated IVF cycles. Eur. J. Obstet. Gynecol. Reprod. Biol., 75, 215220.[ISI][Medline]
Noci, I., Biagiotti, R., Maggi, M. et al. (1998) Low day 3 luteinizing hormone values are predictive of reduced response to ovarian stimulation. Hum. Reprod., 13, 531534.