Dexamethasone When Added to Ovulation Induction Drugs Improve Ovarian Response of Women

مجلة بابل الطبية- المجلد التاسع- العدد الول- Medical Journal of Babylon-Vol. 9- No. 1 -2012 201 2

Dexamethasone Improve Ovarian Response to Ovulation Induction Drugs in Women Over 35 Years

Suhaila F. Al-Shaikh College of Medicine, University of Babylon, Hilla, Iraq.

Abstract Background: With aging, the ovarian reserve is decreased and that is a major contributor to poor ovarian response to ovulation induction treatment. The aim of the present study is to evaluate the role of Dexamethasone on ovarian response in infertile patients aged over 35 years. Materials and Methods: In this study, a total of 36 infertile women over age 35, referred to Babylon hospital-infertility clinic from May 2010 to may 2011 were selected. Ovulation induction was initiated for them using HMG (human menopausal gonadotrophin) for 2 consecutive cycles then after excluding 10 women Dexamethasone co-treatment (1mg/d) was started ( in 26 women ) in their next menstrual cycle. It was started on the 21st day of the menstrual cycle and continued until CD12 together with the HMG (from CD 2-12) of the next cycle. The main outcome measures were number of mature follicles detected by U/S, number of used HMG ampoules/cycle , and serum E2 level on HCG injection day. Results: There was no significant statistical difference in age, duration of infertility, hormonal tests, and number of mature follicles. However, the number of used HMG ampoules was significantly lower in Dexamethasone used cycle compared to non-dexamethasone cycles (p<0.05). Conclusion: The addition of dexamethasone 1mg/d to ovulation induction treatment decreased the number of HMG used in patients over 35 years who hold known risk of low ovarian response. الديكساميثازون عند اضافته الى ادوية تحفيز الباضة يحسن استجابة المبايض عند النساء فوق سن الخامسة والثلثين الخلصة مع تقدم العمر بالمراة ينضب لديها احتياطي البيوض في المبايض و هذا يؤدي بالنتيجة الى قلة خصوبتها و ضعف استجابتها للدوية المحفزة للباضة في هذه الدراسة تم تقييم دور دواء الدكساميثازون عند اضافته للدوية المحفزة للباضة تم اختيار 36 امراة فوق سن ال 35 عام ممن يراجعن استشارية العقم في مستشفى بابل للنسائية و الطفال للفترة من مايو 2010 الى مايو 2011 في البدأ و بعد اجراء الفحوصات اللزمة واخذ موافقتهن تم اعطءهن المحفزات الهرمونية (الهرمون المحفز للبويضة )ابتداء من ثاني يوم للدورة الشهرية مع مراقبة الستجابة للتحفيز عن طريق مراقبة حجم البويضة بواسطة جهاز الفحص بالمواج فوق الصائتة المهبلي وفحص نسبة هرمون السترادايول. و تم تكرار نفس العلج للشهر الثاني على التوالي و بزيادة جرعة الهرمون المحفز للبويضة. و بعد استثناء 10 نساء (6 بسسب نجاح الحمل و 4 لم يتابعن العلج) أي ان المجموعة الجديدة 26 امرأة تم اخضاعهن للطريقة العلجية الخرى باستخدام الدكساميثازون مع الهرمون المحفز للبويضة مع الستمرار بمراقبة الستجابة للعلج بواسطة فحص حجم البويضات بجهاز الفحص بالمواج فوق الصائتة المهبلي وفحص نسبة هرمون السترادايول. النتائج: لم يكن هناك فرق احصائي واضح في عدد البيوض الناتجة من التحفيز و لكن كان عدد الحقن المستخدمة من الهرمون المحفز للبويضة اقل في المجموعة التي استخدم فيها دواء الدكساميثازون مع عملية التحفيز و بشكل مهم احصائيا

Suhaila F. Al-Shaikh 209 مجلة بابل الطبية- المجلد التاسع- العدد الول- Medical Journal of Babylon-Vol. 9- No. 1 -2012 201 2

الستنتاجات: عند اضافة الدكساميثازون لعملية تحفيز الباضة بواسطة الهرمون المحفز للبويضة يؤدي الى الحصول على عدد جيد من البيوض ولكن بعدد اقل من حقن الهرمون المحفز مما يدل على استجابة المبايض بشكل افضل بعد اضافة دكساميثازون لعملية التحفيز وكذلك تكون التكلفة لعملية التحفيز (أقل) نظرا لرتفاع ثمن الهرمونات المحفزة للبويضات. Introduction Glucocorticoids can indirectly improve oor ovarian response to the response of poor responders by exogenous gonadotropins is one increasing serum levels of GH [18] and Pof the challenges of assisted IGF-1 [19] and by consequently reproductive technology that occurs in increasing intrafollicular concentration 9-26% of cycles [1] and may interrupt of IGF-1. To date, the IGF-1 mRNA the cycle causing less available oocytes has not been detected in human and an eventual decrease in pregnancy granulosa cells prior to ovulation and it rate [2]. Advanced age, prior ovarian seems to be derived from circulation surgery, pelvic adhesions, and high [19]. body mass index (BMI) are all In the study of Jenkins and associated with poor ovarian response; colleagues, following pituitary however, poor response is also noted in suppression in IVF cycles, co- young women [1, 3]. With aging, the treatment with dexamethasone resulted ovarian reserve is decreased and that is in an increase in serum IGF-1 levels a major contributor of poor ovarian and growing follicle [20]. On the other response to exogenous gonadotropins hand, Dexamethasone impoved ovarian [4]. There are several reports about responsivness by diminished effect of other potentially effective adrenal androgens on follicular growth gonadotropin based treatment methods [21]. In another study Kemeter and including high dose gonadotropin colleagues found higher pregnancy regimens [2, 5, 6] and co-treatment rates in prednisolone group compared with growth hormone (GH) [7, 8] to control [22]. Also, in a study by glucocorticoids [8-10], and low dose Keay et al, co-treatment with aspirin [11]. dexamethasone reduced the incidence Moreover, it is possible to estimate of poor ovarian response [12]. In the the ovarian response by measuring the light of these results this study tries to serum levels of GH during normal and compare the effect of dexamethasone ovulation induction cycles. Inadequate on ovarian response in infertile women stimulation of the somatotropic axis over 35 with a control group. may lead to poor ovarian response [12]. The ovarian response to Materials and Methods gonadotropins is regulated by IGF-1 In this study a total of 36 infertile (insulin-like growth factor 1) that has women over age 35 years were studied an in vitro positive feedback on FSH during may 2010- may 2011. via granulosa cell receptors [13, 14]. The inclusion criteria comprised age The effect of treatment with GH, L- over 35 , Women with endocrine Arginine and pyridostigmine as disorders (thyroid, hyperprolactinemia, adjuvants in poor responders have been etc), endometrioma and history of studied [15-17]; all three act on the ovarian surgery , women with tubal somatotropic axis. Both L-Arginine factor and couples with male factors and pyridostigmine significantly infertility were excluded. oral consents improve ovarian and intrafollicular obtained from all patients. All patients concentrations of IGF-1 [12]. (36 women (control group)) received

HMG injections from cycle Day 2 (1 The mean numbers of mature ampoule/day 75 IU) with u/s follicles were 2.27 + 1.5, 1.83 + 1.4 in monitoring of the follicles on every 1st and 2nd group respectively other day until a leading follicle of 16 However, the number of HMG mm was detected and the process was ampoules used in two groups varied repeated with higher doses of HMG in significantly (20.6 + 5.39 in 1st group the next cycle ( 2 ampoules 150 IU / vs. 26.65 + 6.34 in 2nd group; p<0.05) day) . then the ovulation induction was (Table 2). repeated for the same women with addition of dexamethasone (10 women Discussion are excluded in this treatment because Several studies have shown the 6 get pregnant and 4 women were lost effect of low dose dexamethasone on from follow up ) so 26 patients improvement of ovarian (treatment group) received a daily oral responsiveness at the initiation of dose of 1 mg of Dexamethasone (Tab, induction of ovulation cycles [12, 23]. 0.5 mg). Dexamethasone co-treatment However, controversy still exists in was started on the 21st of their this regard. In this study, the number of preceding menstrual cycle and it was mature follicles did not differ continued until CD12. gonadotropin significantly between the therapy ( HMG) 2 ampoules 150 IU/ dexamethasone and non day) from the CD2 was continued up dexamethasone groups. These findings to the day when a leading follicle of 16 are consistent with some prospective mm detected then hCG was randomized trials performed administered. Follicular development previously [12, 23]. Keay et al was monitored by serial transvaginal randomized 290 patients under 40 ultrasonography. years undergoing IVF/ICSI cycles and The number of mature follicles, reported that treatment with 1 mg injected HMG ampoules, and the levels dexamethasone daily could not of estradiol on the day of hCG improve the number of retrieved injection, were compared in the two oocytes significantly [12]. In another groups. The data were analyzed using study, they administered 10 mg the two-tailed Student’s t, and Fisher’s prednisolone to PCOS patients treated exact tests. Data were expressed as with IVF and found no significant means ± SD and p<0.05 was increase in the number of aspirated considered as statistically significant. oocytes [23]. In the current study, the number of HMG ampoules used in Results patients treated with dexamethasone There were 26 women in the(1st) was significantly lower than that of the treatment group (when dexamethasone non-dexamethasone group. was added to the treatment) and 36 the number of used HMG ampoules women (2nd) (control group) (non that is in turn a determining factor in dexamethasone treatment group). The the assessment of ovarian response to mean age, duration of infertility, FSH, gonadotropins was significantly lower LH and estradiol and testosterone of in dexamethasone group than the the second day of cycle (Table 1). second group. This can explain the role None of these variables showed of dexamethasone in increasing significant difference between the two ovarian response since follicular groups. growth could be obtained with less amounts of gonadotropins. The reason for a lack of difference in the number

of mature follicles in two groups may ampoules used in Dexamethasone be the fact that these numbers are group was significantly lower than the directly related to the ovarian non-dexamethasone group. This functional reserve and in aged women difference may imply the positive (> 35 years) whose reserves have been effect of Dexamethasone on ovarian reduced [3], one cannot reach a high response to gonadotropins so that number of oocytes despite the utilization of this drug as an adjuvant prescription of dexamethasone. for standard treatment is recommended in patients over 35 years who hold Conclusion known risk of low ovarian response Although there was no statistical and also yield lower cost for the difference between number of mature treatment cycles. follicles but the number of HMG

Table 1 Demographic and clinical characteristics of the Dexamethasone treated patients and controls

Dexamethasone Characteristic Treatment group Control Group (n=36) P Value (n=26) (Mean+SD) (Mean+SD)

38.55+3.54 36.55+4.54 Age (Year) NS

Duration of Infertility 13.55+7.29 12.55+6.29 ((Year NS

Serum FSH level on 8.76+3.12 7.79+3.42 day 2 (mlU/ml) NS

Serum LH level on 5.12+2.73 6.66+3.67 day 2 (mlU/ml) NS

Serum Estradiol level 100.6+22.1 95.5+27.4 on day 2 (Pg/ml) NS

Total Testosterone 0.4+0.38 0.44+0.2 level on day 2 (ng/ml) NS

Table 2 treatment outcomes in studied groups.

Treatment group Control Group Characteristic P Value (n=26) (n=36) (Mean+SD) (Mean+SD)

Serum Estradiol level at the day of 486.85+271.17 539.64+345.3 HCG injection NS (Pg/ml)

No. of mature follicles 1.5 + 2.27 1.4 + 1.83 NS

No. of HMG 20.6+5.39 26.65+6.34 ampouls used <0.05

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