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reasons for accepting a donated chromosome complement. Ourpreliminary experience demonstrates that fertilised ova of advancedmaturity can readily be recovered and transferred with minimalexposure to tissue culture conditions, and that pregnancy can beobtained. This preliminary experience suggests that transferefficiencies obtainable from ovum transfer may be higher than thosenow widely reported for in vitro fertilisation.

Division of Reproductive Endocrinology,Department of Obstetrics and Gynecology,Harbor-UCLA Medical Center,Torrance, California 90509, USA

JOHN E. BUSTERMARIA BUSTILLOIAN H. THORNEYCROFT

JAMES A. SIMONSTEPHEN P. BOYERS

JOHN R. MARSHALL

Fertility & Genetics Research, Inc,Chicago, Illinois

JOHN A. LOUWRANDOLPH W. SEEDRICHARD G. SEED

EFFECTIVE PROPHYLAXIS WITH ORALANTICOAGULANTS AND LOW-DOSE HEPARINDURING PREGNANCY IN AN ANTITHROMBIN III

DEFICIENT WOMAN

SIR,-Your May 7 editorial on the treatment of familialantithrombin III (ATIII) deficiency states that little information isavailable on prophylaxis with oral anticoagulants and heparinduring pregnancy. We wish to report a case of a 20-year-old womanwith a familial ATIII deficiency. Her ATIII level before pregnancywas 55% (chromogenic substrate S-2238 Kabi, as described by0. R. 0degaard and A. N. Teien, Thromb Res 1976; 8: 1973).Normal values are 80-120%. ’

Despite a family history of venous thrombosis and pulmonaryembolism, she herself had no such episode. Since she wasconsidered to be at high risk group of thrombosis subcutaneous lowdose heparin was started (5000 units twice daily) at the I lth week ofpregnancy; from the 15th week oral anticoagulant was given, and atthe 37th week low dose of heparin was reintroduced until afterdelivery. The levels of anticoagulation were around 12% (normal8—15%, ’Thrombotest’; Nyegaard) and AT levels varied during thegestational period around 55%, showing neither decrease duringheparin nor increase during oral anticoagulant therapy.There was no thromboembolic complication of the pregnancy or

labour and she was delivered ofa normal healthy baby. She was thenprescribed oral anticoagulants for 3 months.These data demonstrate that the combination of oral

anticoagulants and low-dose heparin might protect againstthrombosis during pregnancies in ATIII-deficient women.

Division of Haematology,Department of Medicine,University Hospital,9713 EZ Groningen, Netherlands

E. VELLENGAG. W. VAN IMHOFF

Department of Obstetrics,University Hospital, Groningen J. G. AARNOUDSE

TSH AND ORBITAL ANTIBODIES

SIR,-Although it is generally accepted that Graves’

ophthalmopathy is immunologically mediated the underlyingmechanisms are poorly understood. One theory, derived from thework of R. J. Winand, L. D. Kohn, and their colleagues, is thatthyroid-stimulating hormone (TSH), or "exophthalmogenicfactor", in association with abnormal immunoglobulins in theserum of patients with Graves’ ophthalmopathy, binds to eyemuscle membranes thereby initiating a progressive inflammatoryreaction. We have identified a circulating autoantibody against aneye-muscle-derived soluble antigen in patients with Graves’

ophthalmopathyl and have tested the effect of TSH on the

reactivity of this antibody with eye-muscle-derived soluble antigenand on the reactivity of monoclonal antibodies with antigens in

1. Kodama K, Sikorska H, Bandy-Dafoe P, Bayly R, Wall JR. Demonstration of acirculating autoantibody against a soluble eye muscle antigen in Graves’

ophthalmopathy. Lancet 1982; ii: 1353-56.

human eye muscle and guineapig harderian gland. Thecharacteristics of these antibodies have been described previously. IImmunoreactivity was determined by standard enzyme-linked

immunosorbent assays. TSH had no significant effect on reactivityof monoclonal antibodies with their corresponding antigens whentested over the range 0-250 mU/ml. Representative results aregiven in fig 1, which shows the effects of TSH (incubated withantibody and antigen) on the reactivity of monoclonal antibody64-22 with harderian gland cytosol, of 50-24 with eye musclecytosol, and 50-24 with eye muscle membranes. Although TSHtended to inhibit binding of 64-22 to harderian gland cytosol at lowconcentrations the differences were not significant for any TSHconcentration. The reactivity of monoclonal antibody 50-24 withhuman eye muscle cytosol or membranes was not influenced byaddition of TSH. This was also the case when antigen waspreincubated with TSH, for 60 min at 37°C, before addition ofantibody.Next, effect of TSH on reactivity of serum autoantibodies from

patients with Graves’ ophthalmopathy with human eye-muscle-derived soluble antigen was tested. The results are summarised infig 2. TSH had no significant effect on reactivity of autoantibodies

Fig I-Effect of bovine TSH (0-250 mU/ml) on reactivity ofmonoclonal antibodies with their corresponding human or

guineapig orbital antigens, assessed by ELISA.

Results expressed as optical density. A positive antibody test is takenas an optical density of >0. 25. Antigen concentration was 10 pglml.0-0 = antibody 64-22 (harderian gland cytosol); A - - -A = antibody50-r24 (human-eye-muscle cytosol): w ------1 = antibody 50-24 (humaneye-muscle membranes).

Fig 2-Effect of bovine TSH (0-250 mU/ml) on reactivity of serumautoantibodies from patients with Graves’ ophthalmopathy withhuman eye-muscle-derived soluble antigen, assessed by ELISA.

Results as mean (±SE) optical density (n = 4). A posiuve antibody test is takenas an optical density of>O. 25. Antigen concentration was 100 ng/ml. À-11= TSH incubated (at 4°C overnight) with patient serum. 0- - -0 = TSHpreincubated with antigen (at 37°C for 60 min) before addition of patientserum, A- - -A = TSH incubated (at 4°C overnight) with normal serum,0 - 0 = TSH preincubated with antigen (at 37°C for 60 mm) beforeaddition of normal serum.

I