**1. Introduction**

86 Ectopic Pregnancy – Modern Diagnosis and Management

Visser DS, Fourie FL, Kruger HF. Multiple attempts at embryo transfer: effects on pregnancy

Genetics 1993;10:37–43.

outcome in an in vitro fertilization and embryo transfer program. J Assist Reprod

Disease or damage of the fallopian tubes accounts for 25% to 35% of reported cases of infertility (Pandian at al., 2008). Decreased fecundity may be caused by tubal occlusion, fimbrial damage, and/or peritubal adhesions, usually related to previous pelvic inflammatory disease, endometriosis, pelvic surgery, salpingitis isthmica nodosa or otherwise unknown causes. A special group of women affected by tubal infertility are those who have undergone intentional sterilization; 5% to 25% of these women (Neuhaus et al.; 1995; Kim et al.; 1997; Schippert et al., 2004) later regret having undergone this surgery. Some of them desire an operation to restore fertility, the most frequent reason for this is the desire to have a child with a new partner. The diagnosis of "tubal infertility" is a serious and burdensome diagnosis for the affected woman.

In the presence of a functional impairment of the fallopian tubes, the desire to have a child is (if at all) only possible through complicated, risky and cost-intensive therapies: on the one hand through reconstructive surgery or – on the other hand - by means of assisted reproductive technology procedures (ART). The limitations of surgical repair in many cases have been the driving force behind the rising numbers of ART. However, the success of either treatment - even when attempted multiple times - cannot be guaranteed. Outpatient in-vitro fertilization (IVF) can be repeated several times which results in an overall higher success rate. Unfortunately, a large number of couples is not be able to afford multiple IVF cycles. An IVF therapy also is not without risks and is associated with physical and mental stresses which not infrequently lead to a discontinuation of therapy.

Problems of IVF therapy in many countries, e.g. in Germany, are found in the low birth rates of at most 21% despite a clinical pregnancy rate of approximately 28-30% per embryo transfer, but it is the large number of multiple pregnancies at approximately 20% with occasionally significant maternal and child morbidity and mortality rates. The overall average pregnancy rate in Germany for all IVF cycles in 2009 was 29.5%, compared with a rate of 28.6% for the ICSI cycles (Bühler et al., 2010). Because of German legal restrictions, no embryo selection is permitted and the German Embryo Protection Act, passed in 1991, permits no more than three embryos to be transferred. Oocyte donation as well as surrogate motherhood is illegal.

Ectopic Pregnancy Following Reconstructive, Organ-Preserving Microsurgery in Tubal Infertility 89

In the presence of only mild or moderate tubal pathology, term pregnancy rates of 65% to 80% for salpingneostomy, adhesiolysis and reversal of sterilization have been reported (Marana et al., 2003, 2008; Practice Committee of American Society for Reproductive Medicine, 2008). The ectopic rate for mild disease is reported to be 1%-10% (Boer-Meisel et al., 1986; Winston & Margara, 1991; Nackley & Muasher, 1998), in contrast, EP rates can increase up to 20% to 40% in the presence of intrinsic tubal damage, salpingitis isthmica nodosa and severe tubal pathology (Posaci et al., 1999; Taylor et al., 2001; Pandian et al.,

Microsurgical reversal of sterilization leads to a cumulative pregnancy rate ranging from 40% to 84% and monthly fecundability of 8%-10% (Kim et al., 1997; Land & Evers, 2002), the overall risk of EP appears to be less than 10% (Posaci et al., 1999; Practice Committee of American Society for Reproductive Medicine, 2008). Possible prognostic factors include the type of performed sterilization procedure, the site of anastomosis and the postoperative tubal length (Posaci et al., 1999). Tubal occlusion with rings or clips, isthmic-isthmic anastomosis and a tubal length >5 cm are associated with a greater likelihood of successful pregnancy after resterilization (Practice Committee of American Society for Reproductive

During a retrospective study time of eleven years, 127 women (median age 35.4 years [26- 42]) were refertilized in our clinic after a sterilization was performed before (Figure 1; Figure

The follow-up data of 89 patients could be collected for analysis. The EP rate following the microsurgical reversal of sterilization was 6.7% (6/89 patients), and the intrauterine

Fig. 1. Isthmic-isthmic reanastomosis of the fallopian tube after sterilization (refertilization)

pregnancy rate was 73.0% respectively (65/89 patients) (Table 1).

**2. Methods of microsurgical reconstruction of the fallopian tubes** 

2008).

**2.1 Reversal of sterilization** 

using sutures 8-0 and 6-0 vicryl

Medicine, 2008).

2a and 2b).

Microsurgery of the fallopian tubes to restore functioning in the presence of tubal infertility is a therapeutic standard that has been established for decades. In contrast to IVF therapy, reconstructive surgeries of the fallopian tubes are curative measures. They are performed with the intention of permanently restoring the physiological ability of a woman to have a chance to conceive in every ovulating cycle. After successful surgery, additional spontaneous conceptions are, therefore, possible without renewed therapy. The course of pregnancy and the manner of birth in patients who underwent microsurgery do not differ from childbirth in a normal population. Also with respect to premature births, the rate of cesarean section and multiple births there are no differences versus healthy women who have not undergone surgery.

#### **1.1 Ectopic pregnancy**

Ectopic pregnancy (EP) is a serious and also nowadays a cause of maternal mortality in early pregnancy. The risk factors for EP in general population are pelvic infection, tubal disease, endometriosis, previous tubal surgery, age >35 years and smoking (Thornburn et al., 1986; Tuomovaara & Kauppila, 1988; Dubuisson et al., 1996; Strandell et al., 1999; Bouyer et al., 2003; Clayton et al., 2006; Practice Committee of American Society for Reproductive Medicine, 2008; Gelbaya, 2010). The incidence of EP in general population is approximately 2% (Strandell et al., 1999).

The first pregnancy conceived after ART and embryo transfer was ectopic (Steptoe & Edwards, 1976). The risk factors for ectopic pregnancy following ART with an incidence of 2.1% to 9.4% (Lesny et al., 1999) in all ART patients and up to 11% in patients with tubal infertility (Dubuisson et al., 1991) are reported to be tubal disease, history of pelvic infection (Marcus & Brinsden, 1995; Strandell et al., 1999) and tubal infertility as it is considered to be the indication for ART (Herman et al., 1990; Dubuisson et al., 1991, Verhulst et al., 1993).

In Germany, the overall rate of EP in women undergoing ART procedures from 1999 to 2009 was 2.0% (95% confidence interval [CI] 1.9-2.1) related to all pregnancies with a maximum of 2.2% in the group of women >39 years of age (95% CI 1.8-2.5). 19.9% of all cycles which lead to a pregnancy are done in couples who had an infertility diagnosis of "tubal factor" or "tubal disease". The incidence of EP according to the presence or absence of tubal pathology ranges from 2.3% to 3.7% in the presence of tubal pathology and from 1.7% to 2.1% in women without documented tubal disease. The highest EP rate was detected to be 4.5% (95% CI: 3.0-6.0) related to all pregnancies in young women <30 years who firstly had a tubal pathology, who secondly had been treated with IVF, and who thirdly smoked (original data from the German IVF-Registry, D.I.R. committee´s office, Bismarckallee 8-12, 23795 Bad Segeberg, Germany).

Tubal EP is also a known adverse effect of tubal reconstructive surgery; however the incidence varies widely between 0% and up to 40% depending on the type, location and severity of the tubal disease and the surgical procedure. The success of infertility surgery and the risk for EP depend on the careful selection of appropriate patients.

When compared with the macrosurgical approach, the use of a microsurgical technique has significantly improved the outcome of tubal anastomosis with reduced EP rates (Lavy et al., 1987).

The reconstructive microsurgical techniques should include the following elements (Gauwerky, 1999, Schippert et al., 2010): Atraumatic surgical technique, complete removal of diseased tissue, careful hemostasis, preparation layer by layer and exact adaptation of the tissue structures, complete peritonealization, and continuous irrigation of exposed peritoneal tissue surfaces.

In the presence of only mild or moderate tubal pathology, term pregnancy rates of 65% to 80% for salpingneostomy, adhesiolysis and reversal of sterilization have been reported (Marana et al., 2003, 2008; Practice Committee of American Society for Reproductive Medicine, 2008). The ectopic rate for mild disease is reported to be 1%-10% (Boer-Meisel et al., 1986; Winston & Margara, 1991; Nackley & Muasher, 1998), in contrast, EP rates can increase up to 20% to 40% in the presence of intrinsic tubal damage, salpingitis isthmica nodosa and severe tubal pathology (Posaci et al., 1999; Taylor et al., 2001; Pandian et al., 2008).
