Mohamed Elmahdy MD. Lecturer Obs. Gyn. Alexandria University Egypt Letrozole; New trend in ICSI Mohamed Elmahdy MD. Lecturer Obs. Gyn. Alexandria University Egypt

Endometriosis and ICSI Endometriosis is associated with reduced response and lower results after ICSI/ET. lower number of oocytes Reduced fertilization rate and implantation rates. Bergendal A etal. J Assist Reprod Genet. 1998 Oct;15(9):530-4

Severity and pregnancy rate women with endometriosis have a reduced pregnancy rate 21% for stage I–II 14% for stage III–IV Barnhart K etal. Fertil Steril. 2002 Jun; 77(6):1148-55.

Poor pregnancy rate

Embryos Endometrium Decrease aromatase mRNA in granulosa cells ( Lu x 2012) Donor oocytes from endometriotic patients had bad outcome. (Garcia 1999/ Simon C 1994) Decrease integrin expression in endometrium (Lessey BA 1994) Decrease leukemia inhibiting factor expression in the endometrium ( Tabibzadeh S 2000) Abn. Progesterone receptor expression in endometrium. ( Lessey BA 1996) ↑ VEGF A ( Donnez 1994)

Cochrane review protocol The administration of GnRH agonists for a period of three to six months prior to IVF or ICSI in women with endometriosis increases the odds of clinical pregnancy by fourfold. Cochrane Database Syst Rev 2006; 25:1. Another published Issue in 11, 2010.

Is it suitable for poor responders or minimal and mild endometriosis?

Basic pathology of estrogen biosynthesis in endometriosis. X

Letrozole

advantages accumulation of intraovarian androgens and up-regulation of estrogen receptors augment follicular sensitivity . short half-life. Biol Reprod; 1997. 57,514–519.

Aromatase inhibitors in IVF One pilot study in 2009 had shown a protocol for ICSI by combined down regulation by aromatase inhibitor and GnRH agonist in endometriosis. The number of oocytes retrieved was 7.5 (6.0-10.0) and the fertilization rate was 0.78 (0.38-1.0). Five (25%) had a clinical pregnancy. Eur J Obstet Gynecol Reprod Biol. 2009 May;144(1):48-53.

histopathology histological diagnosis should be done only for diagnosis of activity not to confirm. (GPP) No yes

Aim of the study evaluate the effect of Aromatase inhibitor on the outcome of ICSI in women with minimal to mild endometriosis.

Study design a randomized controlled trial that was conducted on 60 women with minimal and mild endometriosis seeking for fertility at Alexandria university ICSI center.

Patients females seeking for fertility due to minimal and mild endometriosis, at fertility clinic, Alexandria University and fulfilling the following criteria: Age less than 37 years. Basal serum FSH less than 10 IU Minimal to mild endometriosis as diagnosed by laparoscopy and lesions classified according to the revised American society for reproductive medicine scoring.

Exclusion criteria include Potentially Poor responders (basal FSH˃ 10, low antral follicular count). Previous ovarian surgery. Moderate or severe endometriosis according to the revised American society for reproductive medicine scoring. Sever form of male factor infertility

Diagnostic laparoscopy To fulfill the inclusion criteria. Biopsies were taken with a 5-mm biopsy forceps and scissor. Peritoneal biopsy resulted in a specimen 3—4 mm in maximum dimension, which were immediately placed in formalin.

Histopathological examination Standard haematoxylin and eosin stains were performed on all specimens. Endometriosis was diagnosed by the presence of both endometrial glands and stroma. Then activity of the lesions is diagnosed by predominance of stroma.

Randomization procedure Randomization was done according to closed envelopes.

Treatment plan

Study group 30 case HMG+ FSH letrozole Triptorelin 0.1 After 5 days Complete suppression

control group 30 cases HMG+ FSH Triptorelin 0.1 HCG SUPPRESSION

Luteal phase support 200 mg intramuscular progesterone ampoules (prontogest® IBSA) in the first week then 100 mg daily. 400 mg rectal or vaginal progesterone suppository (prontogest® IBSA) daily after the first week.

3 cases were cancelled in the study group and all were in the non active group. On the other side 2 cases were cancelled from the control group. 2 cases were dropped from histopathology in the control group.

Activity through age

Days of stimulation

There was no significant difference in the number of oocytes or the fertilization rate between active and non active groups.

long agonist + letrozole Randomized patients n=60 Group 1 long agonist + letrozole n= 30 active lesions n= 11 pergnancy 4 non active lesions n= 16 pregnancy Group 2 long agonist n=8 3 n= 18 6

Conclusions Activity of lesions decreases by age. Activity of lesions affects the quality of embryos. Letrozole suppress the activity of the lesions and may improve the quality of embryos.

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