**6. Discussion**

106 Enhancing Success of Assisted Reproduction

2. Oligozoospermia (moderate and

3. Insufficient number of embryos

4. Homocysteine in blood of more than 15 nM/l (on the 1st point of

7. ETP more than 1900 nM/min (2nd

8. Peak thrombin more than 360 mM/l

1900 nM/min in the 2nd point of observation)

observation)

fibrinolysis (n = 98)

Criterion Failure of IVF (n=56) Success of IVF

1. Hyperstimulation (early stage) 10 17,8 0 0 0,004

severe) 22 39,3 4 9,5 < 0,001

transferred in IVF cycles (1-2) 18 32,1 5 11,1 0,029

5. Difficult embryo transfer 19 33,9 6 14,2 0,035 6. Defective embryo 18 32,1 5 11,1 0,029

point of observation) 39 69,6 17 40,5 0,006

(for 2nd point of observation) 42 75,0 19 45,2 0,003

**Figure 4.** Analysis of the effectiveness of different therapies with excessive thrombin generation (ETP to

The data in Figure 4 show that the high generation of thrombin and IVF failure is more

common in the course of isolating IPC and less - in combination therapy.

**Table 15.** Causes for the failure of IVF under conducted therapeutic correction of hemostasis and

(n=42)

17 30,3 4 9,5 0,039

Abs. % Abs. %

P-value

To sum up the results we note that excessive thrombin generation and a fibrinolytic inhibition fatal reaction (without correction) reduces the effectiveness of IVF and has a comparable value compared to the traditional risk factors of reproduction. Thus, our study proves a number of recent statements devoted to this problem (Martinez-Zamora et al., 2011; Meltzer et al., 2010; Nelson & Greer, 2008; Rova et al., 2012; Westerlund et al., 2012). However, we have made further progress due to suprathreshold values of laboratory parameters which allow to monitor the increased propensity to blood clotting and / or hypo fibrinolysis and therefore to identify patients with high risk of IVF failure in order to conduct therapeutic correction of disorders . In particular, by the calibrated test of thrombography administration of dalteparin was authorized by its indicators (ETP, Peack thrombin) to lead to the effective reduction of thrombin generation as well as the significant increase in positive outcomes of IVF (6.4 times).

We first proposed and tested method and mode of correction hypo fibrinolysis IPC for women in a cycle of IVF. It was shown that vases compression in these cases leads to the increased activity of t-PA and reduced PAI-1 activity, which is clearly manifested by the sharp increase in the calculated EAAF index , accelerated clotlysis time and the increase in the number of positive outcomes for assisted reproductive technology in 3 times. However, there were no obvious reasons to reduce the dynamic activity of PAI-1 during the course of IPC, even though it appeared to be a favorable result of the non-drug therapy. A negative consequence of the IPC was the phenomenon increasing the generation of thrombin which did not have the prior record. The calculations showed that the IPC in all cases should be combined with heparin prophylaxis to obtain the best clinical results. In this publication, combining vases compression with prophylactic doses of LMWH (low molecular weight heparin) really helped to increase the number of pregnancies in 6.5 times. In our opinion, this non-pharmacological approach to correcting hypo fibrinolysis demonstrates great potential for use in a number of clinical situations, including pregnancy period. In this chapter, we do not include the results of vases compression in women with low fibrinolytic activity after IVF in the first 12 weeks of pregnancy. However, the results are encouraging and will be published later.

The leading role of increased thrombin generation and hypo fibrinolysis in negative consequences of this reproductive technology has been proved in comparative evaluation of the significance of the risk factors of IVF failure. Its value appeared to be comparable with such risk factors as ovarian hyperstimulation syndrome, male factor, poor embryo or small quantities, or hard to bear embryos. In the meantime, the range of risk factors and their significance has changed dramatically after the treatment and correction of disorders of hemostasis and fibrinolysis. In particular, the list of relevant factors was reduced significantly to hypo fibrinolysis (rated by EAAF index) whereas indicators of excessive thrombin generation remained, though in less prominent positions. In addition, risk factors such as male factor, insufficient and difficult embryo transfer, as well as their low quality became more significant. The publication indicates the important role of hyperhomocysteinemia in the failure of IVF. As you know, it refers to the controllable risk

factors which can and must be eliminated by recognized medical methods (by taking vitamins B6, B12, folic acid) at pre-gravid preparation.

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