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ASSOCIATION BETWEEN IMPAIRED UTERINE PERFUSION AND INHERITED
THROMBOPHILIA IN PATIENTS WITH UNEXPLAINED INFERTILITY
H. Selman1, C. Valeri1, G. Antonini2, M. Sbracia3, N. Prapas4,5, A. Pacchiarotti1,2
1Praxi Provita, IVF, Rome, Italy
2University of Sapienza, Department of Urologic and Gynaecologic Science, Rome, Italy
3University of Tor Vergata, Department of Urologic and Gynaecologic Science, Rome, Italy
4IVF Unit, Aristotle University of Thessaloniki, Greece
5Iakentro IVF Center, Thessaloniki, Greece
STUDY DESIGN, SIZE, DURATION:
This is a prospective study, in which the patients were computerized
randomization. Between January 2013 and May 2014, 148 consecutive
infertile patients underwent basal uterine arteries Doppler velocimetry
evaluation.
WIDER IMPLICATIONS OF THE FINDINGS:
This study shows that the increase in resistance of the uterine arteries is positively correlated with the presence of at least two gentic polymorphisms for
acquired trombophilia. Knowing these polymorphism allow s to set the correct treatment immediatly and thus avoid treatments that may not work. Also gives
us important informations on the possible therapy to be set during the entire pregnancy.
MAIN RESULTS AND THE ROLE OF CHANCE:
Patients were similar for demographic data ( Table 1). Our results showed a statistically significant association between trombophilic polymorphism
mutations and impaired uterine arteries only with simultaneous presence of two or three mutations: FV Leiden and gene C677T of MTHFR ( 34,69% vs
1,01% respectively in group A and B, P=0,0001); FV Leiden and mutation G20210A of PT gene ( 20,4% in Group A vs 2,02% in group B , P = 0.0003);
gene C677T of MTHFR mutation and FV Leiden and mutation G20210A of PT gene (18,4% in study group vs 3,03% in control group P= 0,0025) and FV
Leiden mutation, mutation G20210A of PT gene and gene C677T of MTHFR mutation (12,24% vs 1.01% in group A and B respectively). All data are
reported in Table 2.
STUDY QUESTION:
The aim of this study was to evaluate the possible association between impaired uterine arteries and genetic polymorphism of trombophilic markers, like
Factor V (FV) Leiden gene mutation, prothrombin (PT) mutation and homozygous mutation of methylenetetrahydrofolate reductase (MTHFR), in patients
with unexplained infertility.
SUMMARY ANSWER:
The polymorphisms taken individually are not sufficient to explain an alteration in blood flow, while combination of these could be the cause of a altered
uterine flow, resulting in failure of the system both in a spontaneous pregnancy in a pregnancy induced by PMA.
WHAT IS KNOWN ALREADY:
Uterine receptivity is one of the most important factors in determining successful implantation. Several studies showed that failure to conceive might be
associated with an increased resistance in the uterine arteries1,2. A reduced pregnancy rate (PR) has been reported in women with impaired uterine
perfusion3.
REFERENCES:
1 Kurjak A and Kupesic S. Ovarian senescence and its significance on uterine and ovarian perfusion. FertilSteril. 1995; 64:532-7.
2 Cacciatore B, Simberg N, Fusaro P, Titinen A. Transvaginal Doppler study of uterine artery blood flow in in vitro fertilization-embryo transfer cycles. FertilSteril. 1996; 66:130-4
3 Battaglia C, Larocca E, Lanzani A, et al. Doppler ultrasound studies of the uterine arteries in spontaneous and IVF stimulated ovarian cycles.. Gynecol Endocrinol. 1990; 4:245-50
Group A
N=49
Group B
N=99
P value
Age
years (mean±SD)
32±3,6 34.5±2.8 NS
BMI 21.8±1.3 22.1±1.7 NS
Cycle length
days (mean±SD)
27.8±1,6 27.6±1.5 NS
Duration of sterility
years (mean±SD)
3.1±1.6 2.5±2.3 NS
TABLE 1. DEMOGRAPHIC AND CLINICAL CHARACTERISTICS
Group A
N= 49
Group B
N=99
P value
FV Heterozygous 8(16,3%) 6(6,6%) NS
FV Homozygous 0 0
PT 2 (4,1%) 2 (2,02%) NS
MTHFR Homozygous 17(34,7%) 27(27,3%) NS
FV + MTHFR 17(34,69%) 1(1,01%) 0,0001
FV + PT 10 (20,4%) 2(2,02%) 0,0003
MTHFR + PT 9 (18,4%) 3(3,03%) 0,0025
FV+ MTHFR + PT 6(12,24%) 1 ( 1.01%) 0,0055
TABLE 2. DISTRIBUTION OF POLYMORPHISM MUTATIONS
PARTECIPANTS/MATERIALS, SETTING, METHODS:
Pulsatility index (PI) were manually calculated and the patients were
divided in two groups: Group A (n=49) with PI> 3 in at least one of
uterine arteries; group B (n=99) with normal uterine arteries. All patient
underwent a screening for the three main trombophilic markers.

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Association Between Uterine Perfusion and Thrombophilia in Infertile Patients

  • 1. ASSOCIATION BETWEEN IMPAIRED UTERINE PERFUSION AND INHERITED THROMBOPHILIA IN PATIENTS WITH UNEXPLAINED INFERTILITY H. Selman1, C. Valeri1, G. Antonini2, M. Sbracia3, N. Prapas4,5, A. Pacchiarotti1,2 1Praxi Provita, IVF, Rome, Italy 2University of Sapienza, Department of Urologic and Gynaecologic Science, Rome, Italy 3University of Tor Vergata, Department of Urologic and Gynaecologic Science, Rome, Italy 4IVF Unit, Aristotle University of Thessaloniki, Greece 5Iakentro IVF Center, Thessaloniki, Greece STUDY DESIGN, SIZE, DURATION: This is a prospective study, in which the patients were computerized randomization. Between January 2013 and May 2014, 148 consecutive infertile patients underwent basal uterine arteries Doppler velocimetry evaluation. WIDER IMPLICATIONS OF THE FINDINGS: This study shows that the increase in resistance of the uterine arteries is positively correlated with the presence of at least two gentic polymorphisms for acquired trombophilia. Knowing these polymorphism allow s to set the correct treatment immediatly and thus avoid treatments that may not work. Also gives us important informations on the possible therapy to be set during the entire pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: Patients were similar for demographic data ( Table 1). Our results showed a statistically significant association between trombophilic polymorphism mutations and impaired uterine arteries only with simultaneous presence of two or three mutations: FV Leiden and gene C677T of MTHFR ( 34,69% vs 1,01% respectively in group A and B, P=0,0001); FV Leiden and mutation G20210A of PT gene ( 20,4% in Group A vs 2,02% in group B , P = 0.0003); gene C677T of MTHFR mutation and FV Leiden and mutation G20210A of PT gene (18,4% in study group vs 3,03% in control group P= 0,0025) and FV Leiden mutation, mutation G20210A of PT gene and gene C677T of MTHFR mutation (12,24% vs 1.01% in group A and B respectively). All data are reported in Table 2. STUDY QUESTION: The aim of this study was to evaluate the possible association between impaired uterine arteries and genetic polymorphism of trombophilic markers, like Factor V (FV) Leiden gene mutation, prothrombin (PT) mutation and homozygous mutation of methylenetetrahydrofolate reductase (MTHFR), in patients with unexplained infertility. SUMMARY ANSWER: The polymorphisms taken individually are not sufficient to explain an alteration in blood flow, while combination of these could be the cause of a altered uterine flow, resulting in failure of the system both in a spontaneous pregnancy in a pregnancy induced by PMA. WHAT IS KNOWN ALREADY: Uterine receptivity is one of the most important factors in determining successful implantation. Several studies showed that failure to conceive might be associated with an increased resistance in the uterine arteries1,2. A reduced pregnancy rate (PR) has been reported in women with impaired uterine perfusion3. REFERENCES: 1 Kurjak A and Kupesic S. Ovarian senescence and its significance on uterine and ovarian perfusion. FertilSteril. 1995; 64:532-7. 2 Cacciatore B, Simberg N, Fusaro P, Titinen A. Transvaginal Doppler study of uterine artery blood flow in in vitro fertilization-embryo transfer cycles. FertilSteril. 1996; 66:130-4 3 Battaglia C, Larocca E, Lanzani A, et al. Doppler ultrasound studies of the uterine arteries in spontaneous and IVF stimulated ovarian cycles.. Gynecol Endocrinol. 1990; 4:245-50 Group A N=49 Group B N=99 P value Age years (mean±SD) 32±3,6 34.5±2.8 NS BMI 21.8±1.3 22.1±1.7 NS Cycle length days (mean±SD) 27.8±1,6 27.6±1.5 NS Duration of sterility years (mean±SD) 3.1±1.6 2.5±2.3 NS TABLE 1. DEMOGRAPHIC AND CLINICAL CHARACTERISTICS Group A N= 49 Group B N=99 P value FV Heterozygous 8(16,3%) 6(6,6%) NS FV Homozygous 0 0 PT 2 (4,1%) 2 (2,02%) NS MTHFR Homozygous 17(34,7%) 27(27,3%) NS FV + MTHFR 17(34,69%) 1(1,01%) 0,0001 FV + PT 10 (20,4%) 2(2,02%) 0,0003 MTHFR + PT 9 (18,4%) 3(3,03%) 0,0025 FV+ MTHFR + PT 6(12,24%) 1 ( 1.01%) 0,0055 TABLE 2. DISTRIBUTION OF POLYMORPHISM MUTATIONS PARTECIPANTS/MATERIALS, SETTING, METHODS: Pulsatility index (PI) were manually calculated and the patients were divided in two groups: Group A (n=49) with PI> 3 in at least one of uterine arteries; group B (n=99) with normal uterine arteries. All patient underwent a screening for the three main trombophilic markers.