Evaluation of High-Dose Vitamin A Treatment in Postmolar Patients with Low and Plateauing Serum Human Chorionic Gonadotropin Levels

Uberti, Elza Maria Hartmann; Diaz, Ruth Karina Escobar; Cardoso, Rodrigo Bernardes; Braga, Antonio

doi:10.1055/s-0040-1710302

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Revista Brasileira de Ginecologia e Obstetrícia

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Original Article • Rev Bras Ginecol Obstet. 42 (5) • May 2020 • https://doi.org/10.1055/s-0040-1710302 copy

Evaluation of High-Dose Vitamin A Treatment in Postmolar Patients with Low and Plateauing Serum Human Chorionic Gonadotropin Levels^* * Study conducted at the Trophoblastic Disease Center of ISCMPA, Porto Alegre, Brazil, and was presented at the XIX Biannual World Congress of the International society of the Study of Trophoblastic Diseases (ISSTD), September 21-24, 2017, Amsterdam.

Avaliação de alta dose de Vitamina A em pacientes pósmola hidatiforme, com valores baixos e em platô de gonadotrofina coriônica humana

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

To compare the effect of high-dose vitamin A (HD Vit-A) use during postmolar follow-up of patients with low and plateauing (L&P) serum human chorionic gonadotropin (hCG) levels, from the moment serum hCG plateaued (P-hCG) to the ﬁrst normal serum hCG value (< 5IU/L).

Methods

The present retrospective series case study compared two nonconcurrent cohorts of patients. Control group (CG): 34 patients with L&P serum hCG levels who underwent expectant management for 6 months after uterine evacuation, from 1992 to 2010; study group (SG): 32 patients in similar conditions who received 200,000 IU of Vit-A daily, from the identiﬁcation of a P-hCG level to the ﬁrst normal hCG value or the diagnosis of progression to gestational trophoblastic neoplasia (GTN), from 2011 to 2017. The present study was approved by the Ethics Committee of the institution where it was conducted.

Results

In both groups, the prevalence of persistent L&P serum hCG levels was < 5%. In the SG, hCG levels at plateau were higher (CG = 85.5 versus SG = 195 IU/L; p = 0.028), the rate of postmolar GTN was lower (CG = 29.4% versus SG = 6.3%, p = 0.034) and follow-up was shorter (CG = 14 versus SG = 10 months, p < 0.001). During GTN follow-up, there were no differences in GTN staging or treatment aggressiveness in both groups. High-dose Vit-A use did not have any relevant toxic effect. There were no GTN relapses or deaths.

Conclusion

The limited use of HD Vit-A seems to have a safe and signiﬁcant effect on the treatment of postmolar patients with L&P serum hCG levels and may decrease the development of postmolar GTN in this population.

Keywords
gestational trophoblastic disease; low-and-plateauing serum hCG levels; high-dose vitamin A

Variables	Expectant management (n = 34)	Vitamin A use (n = 32)	p-value
Age, years old¹ 1 Mean (Standard derivation, range);	31.4 ± 9.7 [16-52]	29.5 ± 7.5 [15-44]	0.369^t t Student t test.;
Number of gestations² 2 Median (interquartile);	1 (1 - 2)	1 (1 - 2)	0.89^M M Mann-Whitney test.;
Parity² 2 Median (interquartile);	0 (0 - 1)	1 (0 - 2)	0.065^M M Mann-Whitney test.;
Pre-evacuation hCG level, IU/L² 2 Median (interquartile);	40,600 (285-195,779)	85,854 (741-166,890)	0.829^P P Pearson chi-squared test.
Gestational age at diagnosis, weeks¹ 1 Mean (Standard derivation, range);	11.9 ± 3.8 (5-22)	11.8 ± 4.7 (5-29)	0.947^t t Student t test.;
HM histology - N (%)³ 3 No histological differentiation between complete or partial mole occurred in two cases;			0.479^M M Mann-Whitney test.;
Complete hydatidiform mole	21 (63.6)	21 (67.7)
Partial hydatidiform mole	12 (36.4)	10 (34.5)
hCG level at plateau,IU/L² 2 Median (interquartile);	82.5 (35-207)	195 (61-664)
Interval between uterine evacuation and hCG plateau, weeks	12.7 ± 5.8 [8-38]	9.8 ± 3.4 [5-17]	0.019^t t Student t test.;
Interval between hCG plateau and outcome, days	60 (39-91) [9-160]	50 (35-70) [16-290]	0.374^M M Mann-Whitney test.;
Duration of vitamin A treatment, days² 2 Median (interquartile);	-	40 (30-60)	-
Time to hCG normalization, days² 2 Median (interquartile);	65(44-95)	44 (30-71)	0.327^P P Pearson chi-squared test.
Duration of follow-up, months² 2 Median (interquartile);	14 (11-18)	10 (8-11)	<0.001^P P Pearson chi-squared test.
Required chemotherapy due to GTN - N (%)	10/34 (29.4%)	2/32 (6.3%)	0.034^M M Mann-Whitney test.;

Variable	ChT after expectant management N = 10	ChT after high-dose Vitamin A use n = 02	p-value
Age, years old, mean ± SD,¹ 1 Mean (Standard deviation, range); [min - max]	33.8 ± 9.5 (25-51)	22.5 ± 2.1 (21-24)	0.136^t t Student t test;
Evacuation - N (%)			1.000^P P Pearson chi-squared test;
In the RC	7 (70)	2 (100)
Out of the RC	3 (30)	0
Pre-evacuation hCG level, IU/L, median ± IQA² 2 Median (interquartile);	556.000 (369-1.317.065)	283.663 (193.755-373.571)	0.909^M M Mann-Whitney test.
Gestational age at diagnosis, weeks, mean ± SD,¹ 1 Mean (Standard deviation, range); [min - max]	13.1 ± 1.5 (11-16)	10 ± 0 (10-10)	0.017^t t Student t test;
HM^c histology - N (%)			1.000^P P Pearson chi-squared test;
Complete hydatidiform mole	9 (90)	2 (100)
Partial hydatidiform mole	1 (10)	0 (0)
hCG level at plateau, IU/L, median ± IQA² 2 Median (interquartile);	82.5 (43-409)	658.5 (654-663)	0.030^M M Mann-Whitney test.
Time from evacuation to ChT initiation, weeks, median ± IQA² 2 Median (interquartile);	25 (13.8-28)	16 (16-16)	0.727^M M Mann-Whitney test.
Pretreatment hCG level, IU/L, median ± IQA² 2 Median (interquartile);	90.5 (53.3-314)	3.231 (567-3.231)	0.182^M M Mann-Whitney test.
Occurrence of metastasis - N (%)			1.000^P P Pearson chi-squared test;
No	10 (100)	2 (100)
Yes	0	0
WHO/FIGO prognostic risk score - N (%)			1.000^P P Pearson chi-squared test;
Low risk	10 (100)	2 (100)
High risk	0	0
Treatment - N (%)			1.000^P P Pearson chi-squared test;
Clinical, single-agent ChT	8 (80)	2 (100)
Clinical, multi-agent ChT	0	0
Hysterectomy + single-agent ChT	2 (20)	0
Number of ChT cycles to remission, mean ± SD,¹ 1 Mean (Standard deviation, range); [min-max]	1.8 ± 1.3 (1-5)	2.5 ± 0.5 (2-3)	0.407^t t Student t test;
Lenght of follow-up, months, median ± IQA² 2 Median (interquartile);	48 (15-67)	39.5 (35-44)	1.000^M M Mann-Whitney test.
Occurrence of relapse or death - N (%)	0	0	-

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[1] Address for correspondence Elza Maria Hartmann Uberti, PhD, Rua Anness Dias, 295, 90090-020, Porto Alegre, RS, Brazil (e-mail: elzahuberti@gmail.com).