**6. Section 3**

### **6.1 Diagnosis of an ectopic in IVF**

Pregnancies of unknown location include viable pregnancies, ectopic pregnancies and miscarriages (Condous et al., 2005). Only a small portion of them are high risk pregnancies (Condous et al., 2005) and there is difficulty in diagnosis and management. Serial measurements of hCG and progesterone should be performed on a wait and see approach, in parallel with TVS. Serum hCG increase over 48 h of more than 66% – that is,

an hCG ratio of >1.66 – correlates well with a developing intrauterine pregnancy. The use of discriminatory zone technique (Condous et al., 2005), is currently evaluated for prediction of probability of ectopic pregnancy. By this technique, if an intra-uterine sac cannot be seen on ultrasound scan above the threshold value, then steps must be taken to determine whether the pregnancy is abnormal or ectopic. After that a D&C can be safely performed only when a non-viable pregnancy has been documented by either a serum progesterone level of 15.9 nM or the absence of a rise in serum hCG after 2 days; that is, an hCG ratio of <1.50 (Pisarska et al., 1998).

#### **6.2 Transvaginal ultrasound and hCG levels for prediction**

With the use of TVS, before 35 days a pregnancy could be considered as a pregnancy of unknown location, from 35 to 41 days a pregnancy of uncertain viability and from 42 days a viable intrauterine pregnancy (Bottomley et al., 2009. Time for diagnosis of ectopic pregnancy was 48 days. In case, previous ectopic pregnancies took place, then diagnosis could be made before this time. Viability scans should be deferred until 49 days of gestation with a minimal benefit delaying after that. The addition of abdominal pain and vaginal bleeding ads to ectopic pregnancy risk. Statistical models have been developed, based on the hCG ratio to predict the outcome of pregnancies of unknown location and especially ectopic pregnancies (Kirk et al., 2006), but this is not easily implemented in clinical practice.

#### **6.3 Newer biomarkers for ectopic pregnancy**

Daniel et al, tested for serum sVCAM-1, ectopic and normal pregnancies, but did not found any difference (Daniel et al., 2000).

C. trachomatis antigen and nucleic acid could be found at 33% among ectopic pregnancies tissue even if they are negative for cervical Chlamydia (Toth et al., 2000).

Activin A subunit, type II receptors, follistatin, and iNOS show increased expression within the fallopian tube of ectopic pregnancy patients tested serologically positive for C. trachomatis (Refaat et al., 2009). Especially for iNOS, elevated activity positively correlates with protection from hydrosalpinx formation and prevention of the systemic spread of C. trachomatis. In a clinical setting, Florio et al, found that Activin A levels were significantly lower in spontaneous abortions and intrauterine pregnancies than ectopic ones,and at the cutoff of 0.37ng/ml a sensitivity and a specificity of 100 and 99.6%, respectively, was achieved, for prediction of EP (Florio et al., 2007). From the other side, on a different approach, Kirk et al, found no more discriminatory capacity of Activin A and inhibin than serum hCG levels for ectopic pregnancy in case of a pregnancy of unknown location (Kirk et al., 2009).
