Luteal phase empirical low molecular weight heparin administration in patients with failed ICSI embryo transfer cycles: a randomized open-labeled pilot trial.
BACKGROUND
The pathology underlying recurrent implantation failures (RIF) is not clear and treatment options proposed are generally not evidence based. Although the effect of heparin on trophoblast biology has not been studied extensively, given the available data suggesting a possible beneficial effect of heparin on embryo implantation, we decided to undertake this pilot study.


METHODS
One hundred and fifty women with > or =2 failed assisted reproduction treatment cycles were included in this randomized open-label pilot trial. Participants underwent controlled ovarian stimulation with the long protocol and were randomly allocated to receive 1 mg/kg/day low molecular weight heparin (LMWH) or no treatment in addition to routine luteal phase support (LPS) on the day after oocyte retrieval. LPS and LMWH was continued up to the 12th gestational week in pregnant participants.


RESULTS
There were 26 (34.7%) live births in the LMWH group, and 20 (26.7%) in the control group (absolute difference 8.0%, 95% CI -4.2 to 24.9%, P = 0.29). There were 34 (45.3%) and 29 (38.7%) clinical pregnancies in the LMWH and control groups, respectively (absolute difference 6.6%, 95% CI -9.0 to 21.8%, P = 0.41). Implantation rates were 24.5 and 19.8% in the LMWH and control groups, respectively (absolute difference 4.7%, 95% CI -4.7 to 14.1%, P = 0.33).


CONCLUSIONS
Despite lack of statistical significance, observed relative increase by 30% in live birth rates with LMWH may be regarded as a clinically significant trend necessitating further research on the use of empirical LMWH in women with RIF and possibly in all women undergoing assisted reproduction treatment. Failure to demonstrate statistical significance of the observed treatment difference may be due to limited sample size of this pilot study.
Assisted Reproduction Unit of the American Hospital of Istanbul, Guzelbahce Sokak No 20, Nisantasi, Istanbul 34365, Turkey. burman@superonline.com
B
B
Urman
B
B
Ata
K
K
Yakin
C
C
Alatas
S
S
Aksoy
R
R
Mercan
B
B
Balaban
D000328:Adult; D010064:Embryo Implantation / Q000187:drug effects / Q000502:physiology; D004624:Embryo Transfer / Q000379:methods*; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006801:Humans; D007246:Infertility / Q000628:therapy; D008183:Luteal Phase / Q000187:drug effects*; D010062:Ovulation Induction / Q000379:methods; D010865:Pilot Projects; D011247:Pregnancy; D011256:Pregnancy Outcome; D020554:Sperm Injections, Intracytoplasmic / Q000379:methods*
D006495:Heparin, Low-Molecular-Weight