COMBINED INTRA-ABDOMINAL AND INTRAUTERINE PREGNANCIES AFTER GAMETE INTRAFALLOPIAN TRANSFER

1153 has not been involved in IVF but in 1979 had argued the merits of GIFT and described the technique in a protocol considered by Queen Charlotte’s Hospital for Women, London, when the climate of opinion was not as receptive as it is today.) A 26-year-old woman presented with a 4-year history of primary infertility and had been extensively investigated. She had had 2 years’ treatment by artificial insemination by donor. Her husband had severe oligospermia with a sperm count as low as 0-7 x 106/ml. The antecedent menstrual cycle was manipulated with 20 mg norethisterone twice daily for 13 days and GIFT was achieved mid-week on day 13 of the cycle. The ovary was stimulated under the supervision of the Hallam Medical Centre and J. P., with clomiphene citrate 100 mg daily from days 2-6 and 150 U hMG intramuscularly daily from day 4 to 10. Following follicular monitoring by pelvic ultrasound, ovulation was induced with 5000 U hCG 35 h before oocyte retrieval. The sperm preparation was obtained from a mixture of husband and donor semen by swim-up method and concentration adjusted to give 105 active sperms in 25 ul. At laparoscopic oocyte retrieval on May 15, 1986, eight oocytes were recovered and six were deemed preovulatory. All were individually placed in 10 ml Falcon tubes containing bicarbonate buffered Earle’s medium with 8% heat-inactivated pooled donor serum. They were gassed with 5% COin air from a portable cylinder before sealing and maintained at 37°C in a water bath. Five-puncture laparoscopy was used for egg collection (centrally) and tubal cannulation (two punctures in each iliac fossa). Endotherm grasping forceps (no 8383.33 Richard Woolf, West Germany) were inserted in either iliac fossa to elevate the fallopian tubes atraumatically by grasping the dorsal serosa of the tube just below the fimbrial end. Simultaneous to oocyte identification and preparation a 13 gauge FFP Teflon trochar and cannula (H. G. Wallace Ltd) was introduced by transcutaneous puncture and the cannula was passed into ampullary region of fallopian tube. A Wallace no 1816 embryo replacement catheter terminally loaded with a mixture of 25 ul sperm preparation and two oocytes was advanced through the cannula to about 6 cm along the fallopian tube, where the contents were deposited. The procedure was repeated on the other side. The two oocytes not used were incubated with sperm preparation and frozen at the blastocyst stage. The patient received luteal support with 2000 U hCG on 2 days and 5 days after the procedure. She now has a continuing singleton intrauterine pregnancy of 28 weeks gestation. Since the case described two further patients have been treated similarly and one is now

pregnant.

It would appear from the limited data available, with an estimated 250 pregnancies (delivered and undelivered) to date, worldwide, that GIFT is a safe procedure, free from risks of sepsis, and without an excessive incidence of either miscarriage, multiple pregnancy, or fetal anomaly. It should be considered as the treatment of choice in idiopathic infertility, where the results are better than IVF; if applied to the four categories of infertility described GIFT could be used in the treatment of some 55 % of all cases of infertility.! Clearly more data are required, and this information should come from multicentre trials in progress. Factors such as deposition and sperm/egg mixture as far along the tube as possible, as opposed to deposition nearer the fimbrial end, and atraumatic cannulation of the tubes with very soft polyetherbased catheters may improve success rates. Many district general hospitals have gynaecologists and endocrinologists with interests in infertility who have experience in the induction of ovulation. They also have ultrasonographers who are becoming much more involved in studying ovarian morphology and follicular development and could, with a little further experience and using fixed drug regimens and ultrasound assessment of follicular development, provide adequate follicularphase monitoring. If the gynaecologists are also skilled in laparoscopy and can arrange access to a part-time embryologist (or trained senior technician) they should, with some limited additional training and with a small capital outlay, be able to provide a GIFT service. The embryologist would be responsible for preparing and purchasing media, for egg identification, and for semen preparation (by extending semen study methods with a simple adaptation for swim-up technique). The extra equipment for GIFT would

include: a waterbath (WB150 Lukins), a stereo-dissecting microscope, suction apparatus (Craft/Rocket), a 5% CO2 in air cylinder, grasping forceps, and a 16 G needle for oocyte retrieval. Disposable equipment should include: syringes, petri dishes, Falcon tube, pipettes, and bulbs. This equipment outlay is 2,500. Manipulation of menstrual cycle could time GIFT for morning or afternoon operating lists with some certainty for any weekday t 1 day. Given the above, ordinary theatre facilities will suffice.

We have demonstrated that GIFT

can

be done outside IVF

units, and hope that the information and suggestions provided will foster more

widespread interest in the technique.

We thank the Portland Hospital for their cooperation and assistance in the surgical management of the case, the Hallam Medical Centre for supervision and provision of embryologist and induction of ovulation, and H. G. Wallace Ltd, Colchester, Essex, for providing cannulae and catheters. 48 Wimpole Street, London W1M 7DG

CRITON PAVLOU

Department of Obstetrics and

Gynaecology, Kmg’s College Hospital, London SE5; and Hallam Medical Centre, London W1N

JULIAN PAMPIGLIONE

1. Hull MGR, Glazener CMA, Kelly NJ, et al. Population study of outcome of infertility. Br Med J 1985; 291: 1693-97.

causes, treatment and

COMBINED INTRA-ABDOMINAL AND INTRAUTERINE PREGNANCIES AFTER GAMETE INTRAFALLOPIAN TRANSFER

SIR,--Gamete intrafallopian transfer (GIFT) is becoming an accepted form of treatment for infertility.l,2 Extracorporeal fertilisation is not required and in cases of unexplained infertility it is generally regarded as being superior to in vitro fertilisation and embryo transfer. However, it is not yet possible to be certain about the safety of the procedure. We describe here a complication of GIFT in a 27-year-old woman who had been attempting to conceive for 5 years. Investigations on her were essentially normal and her husband has severe oligospermia and teratospermia. Fifteen attempts at artificial insemination by donor had been unsuccessful. The ovaries were stimulated by clomiphene citrate and human menopausal gonadotropin, and follicular development was monitored by ultrasound. When the leading follicle was 19 mm and the endometrial thickness was 0-9 mm the patient was given human chorionic gonadotropin (HCG). The sperm sample was prepared33 2 hours before the egg collection. At laparoscopy the pelvis was essentially normal and both tubes were healthy. She had two small fundal fibroids and a posterior fibroid about the size of a golf ball. Eight oocytes were colleted and six were used in GIFT, three oocytes mixed with about 20 l of a suspension, containing some 100 000 sperm, being transferred to each tube. The catheter was checked after each transfer. HCG was given on days 2, 5, and 8 after laparoscopy. An ultrasound scan 4 weeks after revealed two intrauterine gestation sacs. 5 days later, however, vaginal bleeding began and a repeat scan revealed only one intrauterine sac. When she was 8 week’s pregnant she had severe lower abdominal pain and dysuria, but there was no more vaginal bleeding. At her local hospital the only abnormality was a raised white cell count (27 000/u.l). Red degeneration of her fibroids was diagnosed and she was treated conservatively. Severe lower abdominal pain, radiating to the vagina and rectum, recurred at 10 weeks. She was still having dysuria. An ultrasound scan revealed an intact intrauterine pregnancy with a fetal crown-rump length consistent with 10 weeks. Examination revealed a distended abdomen with sluggish bowel sounds and rebound tenderness in both iliac fossae. There was tenderness in both fbmices and anterior to the uterus. 12 hours later tachycardia developed and her Hb dropped to 10 4 g/dl. Laparotomy revealed haemoperitoneum, and 1litres of blood was aspirated. The source of the bleeding was a gestational sac attached to the anterior surface of the uterus medial to the left round ligament and extending onto the bladder reflexion and the superior surface of the bladder. Both fallopian tubes were normal and there was no evidence of red degeneration of fibroids. The sac was completely removed from its attaching surface and haemostasis was obtained since the

1154 attachment was loose. Histological examination confirmed the presence of degenerating chorionic villi. The other, intrauterine pregnancy is now continuing normally. To our knowledge, this is the first report of primary intraabdominal pregnancy after GIFT. We cannot say whether an oocyte spilled into the uterovesical pouch or whether the fertilised oocyte escaped from the fallopian tube back to the pouch; the pregnancy may even have resulted from the fertilisation of an uncollected oocyte that was retained in the uterovesical pouch.

values

at

20 and 30 min did

not

show any

Our results suggest that production of prostacyclin by the vascular endothelium of the patients with Beh4;et’s disease under in vitro conditions may be significantly impaired-either by impaired biosynthesis by vascular endothelial cells affected by vasculitis or because of rapid degradation of prostacyclin. Impairment of prostacyclin biosynthesis may contribute to the pathogenesis of the thrombotic complications observed in Behcet’s disease.

H. I. ABDALLA IVF Unit, Cromwell Hospital, London SW5 0TU

K. K. AHUJA N. MORRIS

J. LYNN

1. Asch

RH, Balmaceda JP, Ellsworth LR, Wong PC. Pregnancy after translaparoscopic gamete intrafallopian transfer. Lancet 1984; ii: 1034. 2. Asch RH, Balmaceda JP, Ellsworth LR, Wong PC. Preliminary experiences with gamete intrafallopian transfer (GIFT) Fertil Steril 1986; 45: 366-71. 3. Ahuja KK, Smith W, Tucker M, Craft I. Successful pregnancies from the transfer of pronucleate embryos in an outpatient in vitro fertilisation programme. Fertil Steril 1985; 44: 181-84.

IMPAIRED PROSTACYCLIN SYNTHESIS BY VESSEL WALLS IN BEHÇET’S DISEASE

SIR,-In Behçet’s disease both superficial and deep veins and arteries of all sizes may be affectedl but vessel occlusions and thrombophlebitis have not been explained. We have found significantly reduced plasma levels of prostacyclin (6-keto-PGF) in the venous blood of patients with Behçet’s disease even without thrombophlebitis,2 and have taken our study a stage further by looking at prostacyclin biosynthesis by vascular endothelial cells. We studied 8 patients (7 males and 1 female) with active Behçet’s disease, 3 with thrombophlebitis, and 1 with neuro-Behcet’s disease and 4 healthy adult volunteer staff members (3 males and 1 female). All gave their written consent for forearm vein biopsy and had taken no drugs for at least 4 weeks before. The skin and subcutaneous tissues were anaesthesised and a 1 cm segment of vein was removed from the antecubital fossa by transverse incision, the vein segment was placed immediately in ice-cold Ringer’s solution (pH 7-4) and sectioned into rings within 15 min. Three rings were transferred into fresh Ringer’s solution at 37°C and samples of supernatant were removed during the next 30 min for assay of 6-keto-PGF,,, a stable metabolite of prostacyclin2, by radioimmunoassay (New England Nuclear) and expressed as pg/mm2 endothelium.3. -

significant increases

(p<0’05).

Faculty of Medicine, and School of Pharmacy, Hacettepe University, Ankara; Turkey

E. KANSU G. SAHIN F. SAHIN B. SIVRI I. SAYEK

F. BATMAN

E, Özer FL, Akalin E, et al. Behçet’s syndrome with obstruction of the venae Quart J Med 1972; 162: 151-68. Hizli N, Sahin G, Sahin F, et al Plasma prostacyclin levels in Behçet’s disease. Lancet

1. Kansu

cavae.

2.

1985; i: 1454 3. Preston FE, Whipps S, Jackson CA, et al Inhibition of prostacyclin and platelet thromboxane A2 after low-dose aspirin. N EnglJ Med 1981; 304: 76-79 4. Clark GM, Cooke D, eds. Basic course in statistics. London: Edward Amold, 1984 173-75.

"MAINTENANCE TREATMENT" FOR ACUTE LEUKAEMIA

SiR,—Dr Pritchard and Dr Chessells (Oct 4, p 805) express dissatisfaction with the term "maintenance treatment" for therapy of acute leukaemia in remission. I share this concern, especially since the terminology may have led over the years to some inappropriate treatment strategies. Freireichl has suggested that the post-induction treatment of acute leukaemia be regarded as "adjuvant" therapy. Most, if not all, acute leukaemia patients in remission have micrometastases and need further treatment, but the duration and details of this adjuvant treatment should not be inferred simply because terms such as "consolidation", "intensification", and "maintenance" have been popular in the past. To the extent that certain agents can induce differentiation of leukaemic cells, long-term drug treatment might maintain a state of differentiation with the appearance of continuing remission. In most cases, however, a strategy based on adjuvant treatment, with the details to be sorted out by controlled clinical trials, would seem more

appropriate.

Division of Hematology and Oncology, University of Alabama at Birmingham,

University Hospital, Birmingham, Alabama 35233, USA 1. Freireich

GEORGE A. OMURA

EJ. Oncology. JAMA 1980; 243: 2199

CALCIUM AND BLOOD PRESSURE

SIR,-Dr Grobbee and Dr Hofman’s paper (Sept 27, p 703) seems lack some important information. The higher the intake of salt (NaCI) the higher the losses of calcium (Ca) in urine from dogs’ and man.2 The osmotic diuresis produced by a high salt intake also increases the urinary losses of phosphate/ magnesium, and potassium.3 The explanation for the potentiation of the blood-pressure lowering effect in the group with parathyroid hormone levels (PTH) above the median could be the effect of a higher intake of salt in this group. With the greater losses of Ca, plasma Ca" - will fall; increased secretion of PTH will bring the plasma Cm - - to normal

to

Prostacyclin synthesis by vein segments obtained from Behrefs disease patients and controls. In all four venous samples from controls prostacyclin synthesisis increased over the 30 min of incubation (figure). Prostacyclin generation was much impaired in seven patients with Behçet’s disease. In 5 patients, there was a progressive and notable decline in the biosynthesis indicated by appreciably lower levels after 30 min of incubation. No synthesis was observed in 2 patients and only 1 patient showed increasing prostacyclin synthesis. The differences between pairs of results at 10, 20, and 30 min were compared by Wilcoxon signed rank test (paired).’ In the 4 controls prostacyclin synthesis significantly increased between the 10 min periods (p < 005). However, in the Behçet’s disease the

and again increase the losses of phosphate in urine.’ Thus the metabolism or balance of phosphate may be a crucial "missing link" in the explanation of raised blood pressure. A significant negative correlation between blood phosphate and blood pressure has been reported,S,6and in our study on the metabolic effect of potassium magnesium phosphate in severely obese women,’ there was at baseline a significant negative correlation between plasma