Combined down-regulation by aromatase inhibitor and GnRH-agonist in IVF patients with endometriomas-A pilot study.
OBJECTIVE
The key enzyme in the biosynthesis of estradiol, aromatase, has been demonstrated within endometriosis. Combined administration of aromatase inhibitor and GnRH-agonist may efficiently suppress estrogen biosynthesis through a combined pituitary, ovarian, peripheral and "in situ" action. The aim of this study was to test the concept of combined down-regulation prior to IVF in patients with endometriomas.


METHODS
Prospective pilot study in a university-based tertiary fertility clinic including 20 infertile patients with endometriomas undergoing IVF/ICSI. The patients received goserelin 3.6mg sc on treatment Days 1, 28 and 56, and one daily tablet of anastrozole 1mg from Day 1 to Day 69. Controlled ovarian stimulation was initiated from Day 70. Outcome measures were change in endometriomal volume and serum CA125 during down-regulation, standard IVF parameters including pregnancy and delivery rate, and endocrine response. The paired T test and Wilcoxon Signed Rank test were used to analyse paired differences.


RESULTS
During the combined down-regulation, the endometriomal volume and the serum CA125 level decreased by 29% (3-39%) and 61% (21-74%), respectively (median (95%CI), P=0.007 and P=0.001). In the IVF/ICSI cycle, the number of oocytes retrieved was 7.5 (6.0-10.0) and the fertilization rate was 0.78 (0.38-1.0). Nine patients (45%) conceived, five (25%) had a clinical pregnancy, and three (15%) delivered healthy children (two singletons and one twin).


CONCLUSIONS
Prolonged combined anastrozole and goserelin down-regulation significantly reduces endometriomal volume and serum CA125, and is compatible with IVF pregnancy and delivery. However, a high pregnancy loss was noted.
Lossl
Kristine
K
Copenhagen University Hospital, Rigshospitalet, Blegdamsvej, Denmark. kristineloessl@hotmail.com
Loft
Anne
A
Freiesleben
Nina L C
NL
Bangsbøll
Susanne
S
Andersen
Claus Yding
CY
Pedersen
Anette T
AT
Hartwell
Dorthe
D
Andersen
Anders Nyboe
AN
D000328:Adult; D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018394:CA-125 Antigen / Q000097:blood; D015536:Down-Regulation / Q000187:drug effects; D004359:Drug Therapy, Combination; D004715:Endometriosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005307:Fertilization in Vitro; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D017273:Goserelin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009570:Nitriles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010865:Pilot Projects; D011247:Pregnancy; D011256:Pregnancy Outcome; D011446:Prospective Studies; D014230:Triazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014591:Uterine Diseases / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
D047072:Aromatase Inhibitors; D018394:CA-125 Antigen; D004967:Estrogens; D009570:Nitriles; D014230:Triazoles; D017273:Goserelin; D000077384:Anastrozole; D007987:Gonadotropin-Releasing Hormone