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Predictors For Response To Letrozole As An Ovulation Induction in Anovulatory Infertile Polycystic Ovarian Syndrome Women
Predictors For Response To Letrozole As An Ovulation Induction in Anovulatory Infertile Polycystic Ovarian Syndrome Women
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Women
Fadia J Alizzi a*, Hind Abdul Khaliq Showman a, Hayder A Fawzi b
a
Department of Obstetrics, Gynecology and Infertility, College of Medicine, Al Mustansiriyah
University, Baghdad, Iraq. * [email protected]
b
Department of Pharmacy, Al-Esraa university college, Baghdad, Iraq.
Abstract
To assess the predictive value of different clinical, laboratory, and ultrasound
parameters in Letrozole when used as an ovulation induction in anovulatory
infertile PCOS women. The current study was done in the secondary-referral
infertility clinic in AL-Yarmouk teaching hospital, and Al-Mustansiriyah
medical college. Sixty-seven anovulatory infertile women with the polycystic
ovarian syndrome. Letrozole was given orally on day 2 or 3 of the menstrual
cycle for five days and repeated for three consecutive cycles. The primary
outcome measures were to evaluate the response rate in the form of successful
ovulation and clinical pregnancy. The ovulation rate was (64.2%), with
clomiphene naïve vs. previous clomiphene use; it was 87.5%, 51.2%
respectively, while pregnancy rate was (32.8%), 41.6% with clomiphene naïve
vs. 27.9% with previous clomiphene use. Clinical (age, BMI, Waist
circumference, cycle length and days between cycle, infertility period and type,
previous reproductive outcome, androgen symptom and m-FG score),
laboratory (E2, FSH, LH, testosterone, FAI, FBS, fasting insulin, HOMA – IR,
and AMH) and ultrasound (mean ovarian volume, mean AFC and antral
follicular diameter) parameters were founded to affect ovulation and pregnancy
in different extent. After putting all variables in a scoring system, it was found
that if the patients had > 26 points for the score, it's more likely that the woman
becomes pregnant. A predictive pregnancy score was developed from basic
clinical, laboratory, and ultrasound parameters. It may help the clinician to
individualized ovulation induction protocol in PCOS women; however, external
validation of this system is recommended in a more extensive prospective study.
most of the clinical, ultrasound and different between the women who
hormonal variables are significantly achieved success ovulation vs. those who
No p- Cut
Variables Pregnancy Variables AUC SN SP
pregnancy value point
Number 45 22 - Clinical predictors
Age 28.8 ± 6.0 26.2 ± 3.7 0.031 Days between ≤ 35 –
0.905 70% 96%
Infertility cycles 45
25.2 ± 9.1 15.9 ± 4.5 <0.001
Period Infertility
BMI 28.4 ± 3.9 26.0 ± 1.8 0.001 period 0.875 ≤30 100% 58%
90.9 ± (months)
WC 76.5 ± 8.9 <0.001 BMI 0.837 ≤28.9 100% 75%
17.2
Mean Waist
0.826 ≤92 100% 75%
Ovarian 10.9 ± 0.5 10.4 ± 0.1 <0.001 circumference
Volume Modified FG
0.904 ≤8 84% 83%
Dominant score
20.9 ± 1.6 19.4 ± 0.9 0.001
Follicle Size Ultrasound predictors
ET 7.5 ± 0.6 8.9 ± 0.3 <0.001 Mean ovarian
0.997 ≤10.7 93% 100%
m-FG score 8.3 ± 3.3 6.3 ± 3.5 0.026 volume
109.4 ± Mean AFC 1.0 ≤15 99% 99%
E2 156.5 ± 6.6 <0.001
18.2 Endometrial
0.995 >7.2 98% 100%
FSH 5.2 ± 1.0 5.0 ± 0.8 0.603 thickness
LH 10.9 ± 3.7 7.3 ± 1.8 <0.001 Laboratory predictors
SHBG 36.9 ± 6.0 45.9 ± 7.5 <0.001 E2 0.976 >110 98% 92%
Testosterone 1.8 ± 0.2 1.6 ± 0.1 <0.001 LH 0.970 ≤13.85 100% 83%
Free SHBG 0.810 >35 79% 67%
Androgenic 4.9 ± 1.2 3.5 ± 0.8 <0.001 Testosterone 0.912 ≤1.7 93% 83%
Index Free
FBS 93.8 ± 8.5 91.4 ± 6.6 0.254 androgen 0.869 ≤4.57 81% 83%
Insulin 5.4 ± 2.0 4.2 ± 1.0 0.002 index
HOMA-IR 1.3 ± 0.5 1.0 ± 0.3 0.002 FBS 0.887 ≤92 72% 100%
AMH 6.7 ± 0.8 6.2 ± 0.5 0.001 AMH 0.948 ≤6.8 91% 92%
Mean AFC 15.1 ± 2.5 12.8 ± 0.8 <0.001 ROC: receiver operator characteristic, AUC: area
under the curve. SN: sensitivity, SP: specificity
Ovulation Pregnancy
Variables
OR (95% CI) p-value OR (95% CI) p-value
Clinical predictors
Age 0.939 (0.856 – 1.030) 0.185 0.907 (0.817 – 1.008) 0.070
Days between cycles 0.067 (0.016 – 0.276) <0.001 0.377 (0.195 – 0.727) 0.004
Infertility period 0.775 (0.683 – 0.879) <0.001 0.788 (0.686 – 0.905) 0.001
BMI 0.567 (0.432 – 0.744) <0.001 0.786 (0.647 – 0.954) 0.015
Waist circumference 0.892 (0.845 – 0.942) <0.001 0.924 (0.878 – 0.972) 0.002
Androgen symptoms 0.192 (0.059 – 0.623) 0.006 0.547 (0.155 – 1.930) 0.348
Modified FG score 0.108 (0.033 – 0.355) <0.001 0.850 (0.732 – 0.987) 0.033
Infertility (secondary) 2.812 (1.002 – 7.895) 0.049 2.449 (0.839 – 7.150) 0.101
Previous CC use
Not used 3.750 (0.980 – 14.355) 0.054
Failure Can’t be estimated 4.200 (1.018 – 17.322) 0.047
Resistance Reference
Previous reproductive outcome
Previous pregnancy 3.750 (1.019 – 13.795) 0.047 8.0 (2.237 – 28.605) 0.001
Abortion 2.062 (0.579 – 7.347) 0.264 0.229 (0.026 – 2.047) 0.187
No past pregnancy Reference Reference
Ultrasound predictors
1.9 x 10-14 (4.2 x 10-15 –
Mean AFC 0.001 0.549 (0.382 – 0.788) 0.001
4.3 x 10-8)
Antral follicular 1.7 x 1010 (8.1 x 109 – 1.4 x 109 (8.1 x 108 – 2.5
10 0.001 0.001
diameter 7.8 x 10 ) x 109)
Mean ovarian volume <0.001 <0.001 0.013 (0.001 – 0.177) 0.001
Laboratory predictors
E2 1.204 (1.088 – 1.331) <0.001 38.037 (11.291 – 48.231) 0.001
FSH 0.647 (0.374 – 1.119) 0.119 0.858 (0.486 – 1.514) 0.597
LH 0.425 (0.294 – 0.616) <0.001 0.637 (0.477 – 0.850) 0.002
SHBG 1.220 (1.087 – 1.369) 0.001 1.212 (1.096 – 1.341) <0.001
5 x 10-8 (1 x 10-11 – 2 x 2.2 x 10-4 (1.6 x 10-7 – 5.9
Testosterone <0.001 0.001
10-4) x 10-3)
Free androgen index 0.160 (0.062 – 0.413) <0.001 0.198 (0.085 – 0.464) <0.001
FBS 0.761 (0.666 – 0.870) <0.001 0.963 (0.902 – 1.027) 0.251
Insulin 1.158 (0.858 – 1.563) 0.338 0.528 (0.295 – 0.946) 0.032
HOMA – IR 0.899 (0.282 – 2.861) 0.857 0.062 (0.006 – 0.669) 0.022
AMH 0.014 (0.001 – 0.132) <0.001 0.333 (0.151 – 0.735) 0.006
OR: odds ratio, CI: confidence interval
Patients with no ovulation had no active follicle (so odd ratio for dominant follicle size can’t be calculated)
14. If HOMA-IR < 0.99 give four (Alizzi FJ [11], Amer, et al [22], Palomba, et
Cut Cut
Markers AUC SN SP AUC SN SP PPV NPV
point point
Clinical predictors 0.967 >26 100% 82% 73% 100%
Days between ≤ 35 AUC: area under the curve. SN: sensitivity, SP:
0.730 68% 64%
cycles – 45 specificity, PPV: positive predictive value.,
Infertility NPV: negative predictive value
0.837 ≤18 86% 69%
period
BMI 0.684 ≤28.9 100% 40%
Waist
0.747 ≤92 100% 40%
circumference
Modified FG
0.712 ≤8 82% 51%
score
Ultrasound predictors
Mean ovarian
0.802 ≤10.5 100% 69%
volume
Mean AFC 0.744 ≤13 91% 64%
Dominate
0.801 <19.9 64% 76%
follicle size
Endometrial
0.985 >8.3 100% 91%
thickness
Laboratory predictors
E2 1.0 ≥142 99% 99%
LH 0.809 ≤7 82% 80%
SHBG 0.831 >44 64% 91%
Testosterone 0.796 ≤1.6 73% 73%
Free Figure (2): ROC (receiver operator
androgen 0.844 ≤4.21 82% 76% characteristic) curve of the score to predict
index pregnancy
Insulin 0.724 ≤4.17 95% 49%
HOMA – IR 0.749 ≤0.99 95% 67%
AMH 0.732 <6.8 100% 58%
ROC: receiver operator characteristic, AUC:
area under the curve. SN: sensitivity, SP:
specificity
How to cite:
Alizzi FJ, Showman HAK, Fawzi HA. Predictors
for Response to Letrozole as an Ovulation Induction
in Anovulatory Infertile Polycystic Ovarian
Syndrome Women; Iraqi Journal of Embryos and
Infertility Researches (IJEIR), (2019); 9(1): 89-110.
Doi: http://doi.org/10.28969/IJEIR.v9.i1.r6
© 2019 Author(s)
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