I. Introduction

Gestational trophoblastic diseases (GTD) Comprise a group of interrelated diseases including molar pregnancy, invasive mole, Placental-site trophoblastic tumor, and choriocarcinoma that have varying propensities for local invasion and metastases (Bagshawe, 1976). However in the past, the outcome of disease was disastrous for young patients, modern therapy has resulted in high cure rates (>90%), and preservation of Fertility (Newland et al, 1986).

Since the disease occurs mostly in women under the age of 35 (Kim et al, 1995), most of them desire future pregnancy after treatment. In actuality, 42% to 63% of GTD Patients fear the result of later pregnancies (Berkowitz et al, 1994).

There were limited data concerning the first pregnancy, which might be at greatest risk of genetic damages or teratogenic effects induced by the anticancer drugs (Kim et al, 199).

In this study, we conducted research on the outcome of first pregnancy in patients treated for molar pregnancy and persistent GTT by methotrexate (MTX), actinomycin (ACT-D), etopeside, and several combination chemotherapy regimen.

II. Patients and Methods

From 1998 To 2003, 213 Patients with GTD were treated in valli-e-Asr Hospital. We evaluated subsequent pregnancy after one year remission 123 patients with mole who underwent suction curettage, and had natural cured, and 90 GTT (67 Patients with low Risk, and 23 patients with high risk GTT), who were cured after chemotherapy.

Among 90 patients, 60 (66.6%) were in stage I, 9 (10%) in stage II, 13 (14.4%) in stage III and 8 (8.8%) in stage IV. Patients with low Risk GTT were initially treated with single agent chemotherapy (MTX, ACT-D), and high Risk were treated with a combination regimen consisting of etoposide, MTX, ACT-D, and cisplatinum (EMA-EP) (Newland et al, 1986; Surwit and Childers, 1991). Patients were advised not to become pregnant, for at least one year after completing treatment.

III. Results

Patients age ranged between 20 and 36, averaging 27.5 years. 47 (22.06%) Patients desire for subsequent pregnancy at first year after permission, and 33 (70.2%) women become pregnant within 2 years after permission. Between 1998 and 2003, 213 patients with GTD were treated at our center, 47 patients who were successfully treated, desired future pregnancies. They had 33 (70.2%) subsequent conceptions. 6 (12.7%) women had secondary infertility, and 8 (17%) cases continued contraception, because they were scared of side effects of chemotherapy on their fetus. The pregnancy outcome is shown in Table 1.

There were 20 (60.6%) term live births, 3 (9.09%) premature deliveries, 1 (3.03%) still birth, 4 (12.1%) abortion and ectopic pregnancy was not.

Congenital anomaly occurred in 2 (6.6%) cases, with no particular anomaly detected. Repeat mole observed in 5 (15.12%) of cases ,3 of them had previous molar pregnancy. cesarean section was done in 7 (21.2%) of deliveries. The most common indication for cesarean section was placenta previa that occurred in 7 (21.2%) cases.

The premature rupture of membranes (PROM) occurred in 7 (23/3%) cases, as the most common antepartum complication.

In addition, there were 3 (9.09%) preterm labor, 3 (9.9%) cases of pregnancy – induced hypertension (PIH), 2 (6.6%) cases of third trimester hemorrhage, and 4 (13.2%) postpartum bleeding.

Neonatal sex and weight characteristics are shown in Table 2.

Table 1. Pregnancy outcomes in women with GTD

Outcome	Mole	GTT
	No of cases (%)	No of cases (%)
Total pregnancies	20 (60.6%)	13 (39.3%)
Term delivery	12 (60%)	8 (40%)
Preterm delivery	3 (9.09)	0
Still birth		1 (3.02)
Spontaneous abortion	0	3 (9.9%)
Therapeutic abortion	1
Ectopic pregnancy	0	0
Repeat mole	4 (12.12%)	1 (3%)
Congenital anomaly	0	2 (6.6%)
Cesarean section	6 (21/7%)	1 (7.6%)

Table 2. Neonatal sex and weight

		No of cases	%
Sex	Male	6	26
Sex	Female	17	74
Weigh (kg)	<2	2	8.7
	2-2.5	2	8.7
	2-5-3	3	13.04
	3-3.5	8	34.7
	3.5-4	5	21.7
	>4	3	13.04
Total		23	100

IV. Discussion

Gestational trophoblastic diseases occur more often in women with the age of 20 to 40 years, during which period they can conceive. Since the discovery of effective chemotherapy, most patients even in the setting of widespread metstases attain remission, while preserving fertility. Nevertheless, patients and partners fear related to future pregnancies, especially the possibility of recurrent disease, or fetal anomalies. Therefore data related to subsequent pregnancy outcome after treatment for GTD are essential.

This study Showed that the rates of term and preterm deliveries, still birth, abortion, ectopic pregnancy, and congenital anomalies in former GTD patients, are consistent with the overall average rates. Data from other centers similarly show that the subsequent pregnancy experience in patients treated for GTD, is similar to that of general population (Goldstein et al, 1984; Berkowitz et al, 1994; Kim et al, 1998).

In GTT patients who received anticancer drugs, which are preferentially toxic to rapidly dividing cells, such as developing follicles in ovaries, exists a possibility that anticancer medicine, may affect conceivability or generation of the fetus, and therefore the result of pregnancy are very controversial. In addition infertility associated with ACT-D and vincristine treatment (Rustin et al, 1984), and specific toxicities to gonads caused by etoposide have been reported (Rustin et al, 1996; Matsui et al, 1997). However, several previous studies (Goldstein et al, 1984; Rustin et al, 1984; Surwit and Childers, 1991; Berkowitz et al, 1994; Kim et al, 1998) reported that chemotherapy does not influence later pregnancies. Woolas et al, (1998) did not observe a difference in conception rate or pregnancy outcome between patients who were treated with single agent MTX and those who received multiple – agent chemotherapy. However, as pointed out by Van Thiel et al (1970), most of the mutations are recessive and so, may not be easily detected in the first generation of the patients. Observation over several generations would be required.

None of our patients treated with chemotherapy developed premature ovarian failure. Secondary infertility occurred in 6 (12,7%) cases. However, as reported in another study, it was 4.4% (Berkowitz et al, 1987).

The other fear expressed by patients, is repetition of mole. According to some studies, the rate of repeat mole increases to 1% (Goldstein et al, 1984; Berkowitz et al, 1994). In the present series, repeat mole Occurred in 5 (15.12%) cases, and in GTT patients, accrued in 1 (3%). 3 of 5 patients pregnancies were after two moles. This number of repeat mole could be a result of low socio-economic state of our patients and our hospital is a referral centre for complicated patients.

The only remarkable obstetric complication was placenta previa, as noted by Ross, (1976). This may be the result of the destruction of endometrium by disease itself and repeated curettage. Therefore more attention should be paid to the management of these patients.

Rates related to neonatal sex and weight were similar to these in normal pregnancies, as reported by Song et al, (1988).

V. Conclusions

Patients after successful treatment of GTD can expect a normal outcome in subsequent pregnancies (Soo-Kate KHOO, 2003). In addition, the anticancer drugs used to treat GTT patients may not have harmful effects on later pregnancies. Later pregnancies require careful monitoring with early ultrasound and HCG follow up.

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Research Article