Pregnancy outcomes after chemotherapy for trophoblastic neoplasia

The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women.

Objective

To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy.

Method

Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms “gestational trophoblastic disease” and “pregnancy outcome”.

Results

A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities.

Conclusion

The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

Keywords
gestational trophoblastic disease; hydatidiform mole; choriocarcinoma; chemotherapy; pregnancy; fertility

Study	Patient (n)	Pregnancy(n)	Term [n (%)]	Stillbirth [n (%)]	Abortion and ectopic [n (%)]	Repeat mole [n (%)]	Preterm [n (%)]	Malformations [n (%)]
Rustin et al., 1984⁷7 Rustin GJ, Booth M, Dent J, Salt S, Rustin F, Bagshawe KD. Pregnancy after cytotoxic chemotherapy for gestational trophoblastic tumours. Br Med J (Clin Res Ed). 1984; 288(6411):103-6.	245	368	273 (74.1)	8 (2.1)	55 (15)	-	5 (1.3)	2 (0.5)^ number of malformations / pregnancy.
Song et al., 1988⁸8 Song HZ, Wu PC, Wang YE, Yang XY, Dong SY. Pregnancy outcomes after successful chemotherapy for choriocarcinoma and invasive mole: long-term follow-up. Am J Obstet Gynecol. 1988; 158(3 Pt 1):538-45.	205	355	279 (78.6)	5 (1.4)	28 (8)	-	20 (6.7)	3 (1)^* * Number of malformations / delivery;
Kim et al., 1998⁹9 Kim JH, Park DC, Bae SN, Namkoong SE, Kim SJ. Subsequent reproductive experience after treatment for gestational trophoblastic disease. Gynecol Oncol. 1998; 71(1):108-12.	517	115	89 (77.4)	1 (0.9)	17 (15)	5 (4.3)	3 (2.6)	3 (3.2)^* * Number of malformations / delivery;
Woolas et al., 1998⁶6 Woolas RP, Bower M, Newlands ES, Seckl M, Short D, Holden L. Influence of chemotherapy for gestational trophoblastic disease on subsequent pregnancy outcome. Br J Obstet Gynaecol. 1998; 105(9):1032-5.	680	1,313	1,000 (76.2)	19 (1.4)	190 (14.5)	18 (1.4)	-	18 (1.7)^* * Number of malformations / delivery;
Tuncer et al., 1999¹⁰10 Tuncer ZS, Bernstein MR, Goldstein DP, Berkowitz RS. Outcome of pregnancies occurring before completion of human chorionic gonadotropin follow-up in patients with persistent gestational trophoblastic tumor. Gynecol Oncol. 1999; 73(3):345-7.	43	29	22 (75.9)	-	3 (10.3)	1 (3.4)	3 (10.3)	1 (4.1)^* * Number of malformations / delivery;
Amr et al., 1999¹¹11 Amr MF. Return of fertility after successful chemotherapy treatment of gestational trophoblastic tumors. Int J Fertil Womens Med. 1999; 44(3):146-9.	42	120	94 (78.3)	3 (2.5)	8 (6.8)	-	15 (12.5)	-
Lan et al., 2001¹²12 Lan Z, Hongzhao S, Xiuyu Y, Yang X. Pregnancy outcomes of patients who conceived within 1 year after chemotherapy for gestational trophoblastic tumor: a clinical report of 22 patients. Gynecol Oncol. 2001; 83(1):146-8.	22	22	9 (40.9)	1 (4.5)	1 (4.5)	1 (4.5)	1 (4.5)	-
Blagden et al., 2002¹⁴14 Blagden SP, Foskett MA, Fisher RA, Short D, Fuller S, Newlands ES, et al. The effect of early pregnancy following chemotherapy on disease relapse and foetal outcome in women treated for gestational trophoblastic tumours. Br J Cancer. 2002; 86(1):26-30.	1,532	230	164 (71)	2 (1)	26 (11)	3 (1.3)	-	3 (1.3)^ number of malformations / pregnancy.
Garner et al., 2002¹⁵15 Garner E, Goldstein DP, Berkowitz RS, Wenzel L. Psychosocial and reproductive outcomes of gestational trophoblastic diseases. Best Pract Res Clin Obstet Gynaecol. 2003; 17(6):959-68.	-	581	393 (67.6)	9(1.5)	106 (18)	8 (1.4)	35 (6)	10 (2.3)^* * Number of malformations / delivery;
Matsui et al., 2002¹³13 Matsui H, Iitsuka Y, Suzuka K, Yamazawa K, Seki K, Sekiya S. Outcome of subsequent pregnancy after treatment for persistent gestational trophoblastic tumour. Hum Reprod. 2002; 17(2):469-72.	129	243	169 (69.5)	2 (0.8)	27 (11.1)	5 (2.1)	5 (2.1)	-
Lok et al., 2003¹⁶16 Lok CA, van der Houwen C, ten Kate-Booij MJ, van Eijkeren MA, Ansink AC. Pregnancy after EMA/CO for gestational trophoblastic disease: a report from The Netherlands. BJOG. 2003; 110(6):560-6.	50	21	16 (76)	-	2 (9)	-	2 (9)	2 (11)^* * Number of malformations / delivery;
Matsui et al., 2004¹⁷17 Matsui H, Iitsuka Y, Suzuka K, Yamazawa K, Tanaka N, Mitsuhashi A, et al. Early pregnancy outcomes after chemotherapy for gestational trophoblastic tumor. J Reprod Med. 2004; 49(7):531-4.	137	258	180 (69.8)	3 (1.2)	29 (11.2)	5 (1.9)	5 (1.9)	-
Goto et al., 2004¹⁸18 Goto S, Ino K, Mitsui T, Kikkawa F, Suzuki T, Nomura S, et al. Survival rates of patients with choriocarcinoma treated with chemotherapy without hysterectomy: effects of anticancer agents on subsequent births. Gynecol Oncol. 2004; 93(2):529-35.	50	43	34(79)	0	4 (9.3)	0	0	3 (8.8)^* * Number of malformations / delivery;
Garrett et al., 2008¹⁹19 Garrett LA, Garner EI, Feltmate CM, Goldstein DP, Berkowitz RS. Subsequent pregnancy outcomes in patients with molar pregnancy and persistent gestational trophoblastic neoplasia. J Reprod Med. 2008; 53(7):481-6.	-	631	422 (66.9)	9 (1.4)	7 (1.1)	9 (1.4)	42 (6.7)	10 (2.1)^* * Number of malformations / delivery;
Braga et al., 2009²⁰20 Braga A, Maestá I, Michelin OC, Delmanto LR, Consonni M, Rudge MV, et al. Maternal and perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia in Brazilian women. Gynecol Oncol. 2009; 112(3):568-71.	-	252	172 (68.2)	2 (0.8)	42 (16)	7 (2.8)	6 (2.4)	6 (2.4)^ number of malformations / pregnancy.
Williams et al., 2014²¹21 Williams J, Short D, Dayal L, Strickland S, Harvey R, Tin T, et al. Effect of early pregnancy following chemotherapy on disease relapse and fetal outcome in women treated for gestational trophoblastic neoplasia. J Reprod Med. 2014; 59(5-6):248-54.	1,204	255	174 (68.2)	2 (0.8)	34 (13.4)	3 (1.4)	14 (5.4)	-
Total		4,836	3,490 (72)	66 (1.4)	579 (12)	65 (1.6)	156 (4.7)	89 (2.3)^ number of malformations / pregnancy.

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