Fertility-Preserving Options for Cervical Cancer: Page 2 of 3
Fertility-Preserving Options for Cervical Cancer: Page 2 of 3
Published obstetric data indicate that pregnancy outcomes following a vaginal trachelectomy are quite acceptable. A summary of the published outcomes from the same six series previously discussed, which involved almost 100 pregnancies, recently was updated (Table 2).. One-third of the pregnancies ended in the first or second trimester, yet two-thirds reached the third trimester. Of those, one-quarter of the patients delivered prematurely (< 37 weeks), and three-quarters delivered at term. Another recent review of 16 series involving 161 pregnancies post-trachelectomy yielded similar results.
First-Trimester Losses—Overall, the rate of first-trimester miscarriage is approximately 16%, which is comparable to that found in the general population. Luckily, most miscarriages can be managed expectantly. If a curettage is needed, minimal cervical dilatation should be achieved to avoid breaking the cerclage; if necessary, another cerclage can be placed at the time of the next pregnancy at 14 to 16 weeks of gestation.
In our series, six of the eight miscarriages were managed conservatively, and five spontaneous abortions occurred; one patient required misoprostol, but a curettage was needed because of an incomplete evacuation and subsequent endometritis. Conversely, the other two patients were induced readily with misoprostol; one miscarried spontaneously, and the other required a curettage.
Second-Trimester Losses—The rate of second trimester loss is actually higher than that of the general population (10% vs 4%, respectively), and its management is often challenging. Conservative management should be attempted first, if possible. In our series, the two cases aborted spontaneously; one patient delivered spontaneously at 17 weeks of gestation from chorioamnionitis following a genetic amniocentesis, and the cerclage did not appear to cause a problem.
If the membranes rupture or the cervix opens, a trial of labor induction with misoprostol may be attempted with or without removal of the cerclage to allow vaginal delivery. If this is unsuccessful, a dilatation and evacuation may be performed with or without removal of the cerclage. Ultimately, if the mother's condition deteriorates or if other conservative measures fail, a hysterotomy may be needed.
Third-Trimester Deliveries—Our review of obstetric outcomes from 100 deliveries indicates that nearly two-thirds of the pregnant women in this series have reached the third trimester. Roughly 25% of these have delivered prematurely (ie, < 37 weeks of gestation). Only 10% have delivered with significant prematurity (< 28 weeks of gestation) usually related to perinatal mortality and morbidity. This group contained three sets of twins—a matter of concern, as these pregnancies already are at much higher risk for premature delivery.
Conversely, 75% of the pregnant patients who reached the third trimester delivered at term by elective cesarean section. There is no evidence that the newborns are small for gestational age, as supported by the recent study by Klemm et al, who showed by transvaginal Doppler sonography that the uterine perfusion after radical vaginal trachelectomy remains unchanged.
Technically, the cerclage could be removed, and vaginal delivery could be allowed, but the short and scarred cervix may not dilate well. Further, a tear that occurs at the time of delivery may be difficult to repair or may lead to significant bleeding if it extends up to the uterine vessels. Also, if a patient wishes to have more than one pregnancy, it may be preferable not to remove the cerclage.
It is reassuring to know that it is possible to carry several pregnancies to term following a trachelectomy. Indeed, in our series, 16% of the patients had up to four pregnancies following the trachelectomy.
Preterm Births and Second Trimester Losses—Preterm births and second trimester losses are serious concerns in pregnant women who have undergone radical trachelectomies. Two etiologies have been proposed to explain this phenomenon. The first is mechanical in nature and focuses on the lack of lower uterine segment support caused by a very short cervix and resulting cervical incompetence. The second etiology is infectious in nature and probably more important—a shortened cervix may lead to an inadequate or insufficient mucus plug, which is an important natural barrier against ascending infections. This inadequacy may lead to chronic subacute chorioamnionitis, which eventually activates the cytokine cascade and leads to premature rupture of the membranes; premature labor usually occurs secondarily. It is unclear whether the cerclage itself may be a source of bacterial contamination, although a case of Actinomyces infection associated with the cerclage has been reported.
If the membranes rupture prematurely, usually as a result of an underlying chorioamnionitis, there is no benefit in postponing the delivery after administration of a steroid injection and antibiotics.[25,30,31] Most patients usually begin labor within 48 hours, and delays may increase the risk of neonatal and maternal sepsis. In our series, one newborn died of fulminant Escherichia coli sepsis that might have been prevented if the child had been delivered more rapidly. In cases of premature rupture of membranes in the general obstetric population, expectant management beyond 34 weeks of gestation is of limited benefit, with antibiotic administration beneficial to both the mother and the neonate.[32,33]
Management of Pregnancies Post-trachelectomy—General obstetric literature defines a short cervix as measuring less than 2.5 cm; women with a short cervix have a ninefold increase in the risk of delivering before 35 weeks of gestation. As mentioned previously, women who have undergone trachelectomy have a higher risk of premature delivery, considering that they have very short cervices. There are no published guidelines for managing pregnant women following a radical trachelectomy, and all of the following subjects should be discussed with a perinatal specialist. That said, we recently proposed some basic recommendations based on our experience and largely extrapolated from the literature on premature rupture of the membranes and incompetent cervix in the general obstetric population.[25,35,36]
To reduce the risk of introducing infections, routine cytologies probably should be avoided throughout the first trimester and even throughout the pregnancy, unless there is a particular concern. Sexual intercourse may be a source of infection; patients are advised to avoid coitus from the 20th to the 36th week of pregnancy. The value of routine prophylactic antibiotic use between the 14th and 16th weeks of gestation is unclear, as is Shepherd's recommendation that routine vaginal cultures be performed every 2 weeks throughout pregnancy. In addition, it is not clear whether routine prophylactic steroid coverage (to accelerate fetal lung maturity in view of the higher risk of premature delivery) is warranted.
The issue of the Saling procedure has been debated. According to Mathevet and others, this procedure, which involves complete coverage of the cervix os by advancing a strip of vaginal mucosa over the cervical opening to prevent ascending infection, decreases the rate of preterm delivery. However, the procedure itself, which is usually carried out at 14 weeks of pregnancy, poses some possible complications. We do not perform the Saling procedure on a routine basis; however, we reserve it as an option for women who have had a premature delivery at their first pregnancy.
Digital cervical examinations should be kept at a minimum to reduce the risk of introducing infection; these examinations may be replaced by transvaginal ultrasound (TVU), a technology that has been superior in assessing cervical length. Particularly between weeks 14 and 24 of gestation, serial TVU appears to be a good predictor of preterm delivery in high-risk pregnancies.
Several recent studies have demonstrated that progesterone suppositories are useful in reducing the risk of preterm birth in high-risk women, such as those with a previous preterm birth or those with a cerclage.[41-43] No data on their role and efficacy in pregnant women post-trachelectomy are available, but patients may be offered this option based on the fairly strong data in nontrachelectomy patients. Another potentially valuable option is the intake of fish oil (eg, omega-3) as a source of fatty acid. According to Olsen et al, the tocolytic properties of this supplement are probably mediated by the reduction of prostaglandin activity and can reduce recurrence of preterm delivery.
Clearly, pregnant women who undergo radical trachelectomy are at higher risk of preterm delivery either from a mechanical or infectious etiology. Such patients may be followed by experts in cases of high-risk premature rupture of the membranes or an incompetent cervix.
When radical trachelectomy was initially employed, clinicians and patients had concerns regarding the ability of women to conceive following the procedure. Experience shows that most women can subsequently become pregnant naturally without assisted reproductive technologies.[25,26] Women who do not become pregnant naturally need a thorough infertility evaluation to identify the cause of infertility (eg, an ovulatory problem, tubal factor, endometriosis, male infertility).
If no cause is identified, then the infertility may be related to the cervix secondary to the trachelectomy procedure (eg, cervical stenosis, fibrosis, inadequate mucus production). Many patients with infertility secondary to a cervical cause have conceived successfully following IUI or IVF.[25,30] With IVF, the risk of multiple gestations is particularly hazardous, especially considering an increased risk of preterm birth with twins and the reduced lower uterine support post-trachelectomy. One patient who conceived twins following IVF chose to undergo embryo reduction, and she delivered one healthy baby at term. She subsequently became pregnant spontaneously. In our series, five of the seven patients who could not conceive following the trachelectomy procedure managed to get pregnant either spontaneously or with IUI or IVF.
A history of infertility should not be a contraindication to radical trachelectomy. Some patients with a history of infertility have conceived spontaneously or with the help of assisted reproductive technology after the trachelectomy. Thus, fertility-preserving surgery should not be denied to these patients. Finally, women may not need a complete infertility work-up before undergoing radical trachelectomy, although some patients may wish to do so.
Cervical Stenosis—Cervical stenosis post-trachelectomy is an important issue. Some women may become symptomatic, usually presenting with cyclical abdominal pain and cramps. Cannulation of the cervical canal may be attempted under anesthesia, ideally when the patient is menstruating, to help identify the cervical opening. The cannulation may require the assistance of ultrasonic and laparoscopic assistance to avoid false passage and perforation. The authors were recently successful in cannulating the cervix using small lacrymal probes.
Asymptomatic women may need no additional treatment. If the patient develops infertility problems that are thought to be secondary to the cervical stenosis and cannulation of the cervix, and intrauterine insemination (IUI) cannot be accomplished, in vitro fertilization (IVF) is probably the best option. However, embryo transfer may be difficult. In a recent report, Aust and others recounted their experience with a particularly difficult case. After identifying the cervical opening and dilating the cervical canal, they placed a Malecot catheter in the cervix to keep it open while the patient underwent ovarian induction.
Alternative Surgical Approaches
Because of the natural anatomic accessibility of the cervix through the vagina, the initial surgical technique for the radical trachelectomy, as pioneered by Dargent, favored the vaginal approach. However, the education of surgeons and long learning curve needed to master the technique remains a significant obstacle in the widespread dissemination of the procedure, particularly in North America, where gynecologic oncologists do not frequently perform vaginal surgery. The procedure's popularity and accessibility has suffered from the limited acquisition of skills in laparoscopic and vaginal surgery. To circumvent some of those technical difficulties, alternative surgical approaches have been developed over the past 10 years.