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METHOTREXATE - A NEW ALTERNATIVE IN SELECTED HIGH RISK CASES FOR OPERATIVE ABORTION

Sanjay Rao, V A Hishikar
Dept. of Obstetrics and Gynaecology, Cama and Albless Hospital, Mumbai - 400 001

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In patients with an abnormal uterine anatomy, operative abortion could pose technical difficulties during termination of pregnancy. A medically induced abortion may be the only safe option in such cases. Methotrexate has emerged as a new alternative to operative abortions in patients with high risk factors for operative interference. This study includes the outcome of 26 cases of abortion managed medically with methotrexate therapy in patients with associated high risk factors for surgical interference.

INTRODUCTION

Methotrexate offers an alternative to operative abortion in selected high risk cases for termination of pregnancy. Hence a medically induced abortion using this agent significantly reduces the risk of morbidity and mortality associated with surgical interference.

MATERIAL AND METHODS

Our study of 26 cases was done during a span of eleven months from March 1997 to January 1998. Every patient was individualized and carefully evaluated before selection for methotrexate therapy. Preliminary investigations included a detail case history, clinical evaluation, a complete haemogram including coagulation profile, liver and renal function tests, qualitative b-hCG urine analysis, and ultrasonographic evaluation. The patient’s informed written consent was taken for therapy. Methotrexate was used parenterally in a dose of 1 mg/kg body weight intramuscularly alternate days with a total of 5 doses. Folinic acid was used in a dose of 0.1 mg/kg body weight along with methotrexate therapy. The main contraindications to this therapy included anaemia, leucopenia, thrombocytopenia, presence of acute peptic disease, ulcerative colitis, severe renal or hepatic impairment.

OBSERVATIONS

Table 1
	Diagnosis	No. of cases
1	Congenital malformation of uterus with missed abortion	4
2	Missed abortion with previous caesarean section	7
3	Retained products of conception following incomplete medical termination of pregnancy	4
4	Retained products of conception in cases of MTP with suspected perforation of uterus with a haemodynamic status	3
5	Missed abortion with pelvic infection	6
6	Multiple myomas with missed abortion	2

Table 2
Induction - response interval after initiation of therapy
Duration	No. of cases
Less than 1 week	7
1-2 weeks	8
More than 2 weeks	8
No response after 3 weeks	3

Table 3
Adverse effects	No. of cases
Nausea	17
Vomiting	4
Diarrhoea	2
Headache	2
Abdominal discomfort	11
Oral ulcerations	6
Haematological complications	0
Elevated hepatic enzymes	0

DISCUSSION

Methotrexate is a folic acid antagonist which binds to the catalytic site of dihydrofolate reductase. This interrupts the synthesis of the purine nucleotide and amino acids serine and methionine. The actively proliferating trophoblast is exquisitely sensitive to methotrexate. In cases of missed abortion the dead trophoblast gets destabilized from its attachment to the decidua. Methotrexate interrupts corpus luteum support and progesterone production. The declining levels of progesterone and b-hCG results in loss of pregnancy and eventually causes a medical abortion. [1]

In one present series the success rate was almost 88% probably because therapy was initiated at an early gestational age). [2]

Qualitative b-hCG estimation was negative in urine within 1 week in 60% cases and 2 weeks in 90% cases. 3 cases of abortion (two with previous caesarean section and one with incomplete MTP) did not show any response to therapy and had to undergo a suction evacuation. All patients were serially monitored with quantitative b-hCG estimation, and ultrasonography to evaluate the response. A course of broad spectrum antibiotic was given to every patient. Methylergometrine tablets were given for 5 days to help in expulsion of products with an oxytocic effect. The commonest side effects encountered shown in Table 3, were treated symptomatically. We were fortunate to have no patient developing serious haematological or hepatic complications following therapy.

CONCLUSION

Methotrexate therapy is a promising alternative to surgical management of termination of pregnancies in patients with high risk factors for surgical interference. The success of therapy depends on appropriate case individualisation, serial monitoring, early detection and management of potential complications.

ACKNOWLEDGEMENTS

We thank Dr. (Mrs.) KG Tripathy Supdt. Cama and Albless Hospital for having permitted us to use hospital data for publication.

REFERENCES

1. Crenin MD. Medically induced abortion in a woman with a large myomatous uterus. American Journal of Obst Nov. 1996; 1379.
2. Crenin MD, Vrtting Hoff E. Methotrexate and misoprostol versus misoprostol alone for early abortion; a randomized controlled trial JAMA 1994; 272 : 1190-5.

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