A 38-year-old nulliparous woman suffering from premature menopause was stimulated with oestradiol valerate in order to create an artificial endometrial cycle. Three oocytes were donated by a woman on an in vitro fertilisation cycle and were inseminated with the patient's husband's sperm. These were then transferred into the patient's uterus after the endometrium had been primed with progesterone to change it to the secretory phase. Pregnancy resulted and proceeded well. Gestation was terminated at the 34th week by caesarean section and 2 healthy boys and 1 girl were delivered

Bailie, P

North, C

Wiswedel, K

English

AJOL - African Journals Online

70 SAMJ VOL 76 15 JUL 1989that year, but subsequent work identified it as nicotinamide,part of the vitamin B complex.Sir Hans Adolf Krebs (b. 1900) was a German-bornrefugee from Nazism who became Professor of Biochemistryat Oxford University. He shared the Nobel prize for medicineand physiology in 1953 with Fritz Albert Lipmann (b.1899), who had been a research worker at the Kaiser WilhelmInstitute in Berlin and was also a refugee from the Nazis; heheld professorships at Harvard and the Rockefeller Institute.Krebs discovered the tricarboxylic acid cycle (Krebs cycle), aprocess by which foodstuffs are converted in the living cell tocarbon dioxide, water and energy. He was knighted in 1958.Lipmann's share in the Nobel prize was for his discovery ofco-enzyme A and its role in the Krebs cycle.Sir Ernst Boris Chain (1906-1979) shared the Nobel prizefor medicine in 1945 with Sir Alexander Fleming (1881-1955), a bacteriologist at St Mary's Hospital, London, and SirHoward Walter Florey (b. 1898), a professor of pathology atOxford University. They evolved penicillin, the' first anti-bacterial substance and an antibiotic still freely used today. Itsevolution took 16 years from Fleming's initial observation in1928 that a Penicillium mould contaminating a culture plate ofStaphylococcus liquified the colonies. Sensing that an exuact ofthe mould could be used in ueatment, Fleming attempted toprepare an effective extract bur failed and gave up in 1932.Fortunately in 1929 he had published his findings - as alaboratory curiosity - in the Brirish Journal of ExperimencalParhology. This article was notIced in 1938 by Chain,S whowas a Ph.D. graduate in biochemistry from Berlin and arefugee from Nazi Germany then working in Florey's depart-ment at Oxford. Chain was given the task of investigatingpossible antibacterial substances of microbial origin. Obtainingthe original Penicillium suain from Fleming, the Oxford teamwere able to prepare a crude exuact that protected miceagainst pneumonia but they could not adequately purify theexuact for use in man since the usual methods of exuactioninactivated the penicillin. After 3 years of work under difficultwar-time conditions, Chain succeeded using a chromatographicprocess to purify penicillin; this was proved to be effectiveclinically. Fleming, Florey and Chain received knighthoods.REFERENCES1. Cushing H. The Life of Sir William Osier. London: Oxford University Press,1940: 214-215. '2. Winter S, Levy N. Medicine in Palestine following the flight of Jewishphysicians from Nazi Germany. Adler Museum Bullecin 1986; 3: 19-234.3. Dreyfus C. Some Milestones in the History of Hemacology. New York: Grune& Srranon, 1957: 71-84.4. Bordley J, McGhee Harvey A. Two Ceneun'es of American Medicine, 1776-1976. Philadelphia: WB Saunders, 1976: 247-250.5. Maurois A. The Life of Sir Alerander F1eming. London: Jonathan Cape,1959: 160-171.Pregnancy without ovarian functionA case reportK. WISWEDEL, C. NORTH, P. BAILLlESummaryA 38-year-old nulliparous woman suffering from prematuremenopause was stimulated with oestradiol valerate in orderto create an artificial endometrial cycle. Three oocytes weredonated by a woman on an in vitro fertilisation cycle andwere inseminated with the patient's husband's sperm. Thesewere then transferred into the patient's uterus after the endo-metrium had been primed with progesterone to change it tothe secretory phase. Pregnancy resulted and proceeded well.Gestation was terminated at the 34th week by caesareansection and 2 healthy boys and 1 girl were delivered.S Air Med J 1989; 76: 70-71.Andrology Laboratory, Department of Obstetrics andGynaecology, University of Cape Town and Groote SchuurHospital, Cape TownK. WISWEDEL, M.D. (KIEL), F.CO.G. (S.A.), DIP. MID. CO.G. (S.A.),M.MED. (0. & G.)C. ORTH, DIP. MED. TECH., B.SC (MED.) HO. 'sP. BAILLIE, F.R.CO.G.Accepted 14 Mar 1989.Oocyte donation is indicated either when a patient has non-functioning ovaries or when ovaries are not present. Otherpatients requiring donor oocytes are women at high risk ofhaving children with genetic defects and those in' whomseveral in virro fertilisation (IVF) cycles have not been success-ful in retrieving adequate quality oocytes and in whom ulua-sonography shows that the ovaries are inaccessible to oocytepick-up. Other women who qualify for oocyte donation arethose with congenital defects and patients who suffer from'premature ovarian failure or who have the resistant ovarysyndrome. These women, who constitute approximately 5 -10% of an IVF population, can now be treated by oocytedonation.The first report of a successful pregnancy using this proce-dure was published by Lurjen er al.' in 1984. They establishedand maintained a pregnancy in a patient with primary ovarianfailure using IVF and embryo donation.The main problem in these patients has been to prime theendometrium with exogenous oesuogen and progesterone suffi- .ciently to make it receptive to implantation. With the availabi-lity of 'spare' oocytes from consenting patients in our IVFprogramme and the experience we have gained with primateand human oocyte and embryo donation the abovementionedgroups of patients can now be treated successfully.Case reportA 38-year-old nulliparous patient had been diagnosed as havingpremature menopause at the age of 22 years. She was treatedfor many years with hormone replacement therapy to preventearly bone loss and changes in the lipoprotein metabolism. Onrepeat hormonal screening the luteinising hormone level wasfound to be 44,8 mIU, follicle-stimulating hormone 54 mIUand .17a-hydroxyprogesterone 0,4 mIU; progesterone wasnon-detectable. A chromosomal analysis was repeated and shewas found to be a 46,XX normal female. A laparoscopy wasperformed and this showed a normal size anteverted uteruswith normal fallopian tubes but streak ovaries. Ovarian biopsywas performed bilaterally and histological examination of thespecimens showed no primordial follicles. The antinuclearfactor was negative.A prospective donor was recruited from the IVF programme;she was prepared to donate 3 oocytes should we retrieve morethan 10 at the time of laparoscopy. This donor was matched tothe phenotypic characteristics of the recipient in respect ofcolour of hair and eyes and approximate body build. Thedonor and her spouse consented to this procedure. At thebeginning of the IVF cycle of the donor we started therecipient on oestradiol valerate orally in slowly increasingdoses to mimic a normal proliferative phase (Fig. 1). On day15 of her cycle the endometrial thickness was 13 mm.EMBRYO3000 TRANSFER x 3I2000E,'000ET131\1,'.15005 '0 '5 20CYCLE DAYSOESTRADIOLVALERATEmg 6rrTI:IIJ~.:li:E1--l..-..!...-L...L...J.---..L..:...L::...J....::..L-L....L..JFig. 1. Scheme of oestrogen medication to induce endometrialproliferation.On the day the donor received her human chorionic gona-dotrophin (HCG) injection, the recipient was started on proge-sterone supplementation (medroxyprogesterone acetate) toinduce the endometrium to change into the secretory phase.At laparoscopy 14 oocytes were retrieved from the donor and 3of these were inseminated with the recipient's husband's sperm.All 3 oocytes cleaved after 48 hours into the 4-cell stage andwere transferred mto the uterus of the recipient using aWallace embryo transfer catheter. The recipient's level of thef:l-subunit ofHCG on day 21 of the cycle was 15,7 mIU/l androse rapidly to 95,8 mID/l on day 24 and 920,0 mID/l on day29. Ultrasonography on day 38 of the cycle showed 2 sacs butno fetal hean activity. Ultrasonography was repeated on day45 when a triplet pregnancy was diagnosed with 3 fetal heanspresent.The pregnancy was maintained using rising doses of oestra-diol valerate (increased by 2 mg per week of pregnancy to amaximum of 24 mg daily in the 8th week). At the same timemedroxyprogesterone acetate was also increased to a maximumof 100 mg per day, then reduced from the 8th week ofpregnancy until both medications were fmally stopped by the14th week of pregnancy.SAMT VOL 76 15 JUL 1989 71The pregnancy proceeded well without any hormonal sup-port. During the. 34th week the patient developed pre-eclamptictoxaemia and was delivered by caesarean section at the end ofthis week of 3 healthy babies - 2 boys and I girl.DiscussionOocyte and possible embryo donation opens a completely newdoor in the treatment of infertility. Although the technique ofdonation of male gametes has been successfully applied formany years through artificial insemination by donor sperm(AID), only with the regular successful use of IVF are femalegametes now also available in sufficient numbers to allow foran oocyte donation programme.2-4 The records of only a fewsuch pregnancies have been published world-wide and the onedescribed above is the first for the RSA. Although IVFtechniques have progressed sufficiently to permit access to arelatively large pool of oocytes, there will always be difficultyin retrieving oocytes, which remain less accessible than malegametes.The ethical.and moral problems of this procedure are of thesame magnitude as and comparable with AID, and will there-fore probably be acceptable to the majority of patients. Thelegality of oocyte donation has fortunately been addressedadequately by the latest amendment to the Human Tissue Act,which regulates gamete donation and therefore includes thedonation of oocytes. A child born from this procedure will belegally the child of the consenting parents as defined by theChild Care Act. .From an obstetric point of view it was hoped that thispregnancy would proceed without major problems to an ad-vanced stage of gestation. This feeling was supported by thefact that it now seems certain that relaxin is produced by theovary··5 and in a patient with non-functioning ovaries therelaxin level should stay low and not cause softening anddilating of cervix during pregnancy; in a multiple pregnancyparticularly this might induce premature labour. Our patientwas delivered by caesarean section because of rapidly develop-ing pre-eclamptic toxaemia while the cervix was still closed.From a pharmacological point of view it is known thatoestradiol valerate has no known teratogenic effects on thefetus and that medroxyprogesterone acetate is not converted toits androgenic precursors and therefore should not have anyandrogenic effects on female offspring. If this procedure wasused on a regular basis, a natural progesterone, which unfortu-nately is not available in this country, would be preferable tomedroxr,pr.ogesterone. The form of progesterone used by otherauthors' IS the natural product and is administered in theform of vaginal pessaries in doses of up to 200 mg!d.It is concluded that oocyte donation closes the last gap inthe treatment of female infertility. The minimal preconditionis that the woman have a receptive uterus.REFERENCES1. Lutjen PJ,Trounson AP, Leeton J. The establishment and maintenance ofpregnancy using in viero fertilization and embryo donation in a patient withprimary ovarian failure. Nature 1984; 307: 174-175.2. Lutjen PI, Trounson AP, Leeton J, Findlay J, Wood C. Pregnancyestablish-ment and malOtenance in the absence of ovarian function. Proceedings of thelth International Gungress of Endocrinology. Quebec, 1984.3. Formigli L, Formigli G, Roccio C. Donation of fertilized uterine ova toinfertile women. Fertil Steri11987; 47: 162-165.4. Weiss G, O'Byme EM, Steinetz BG. Relaxin: a product of the humancorpus luteum of pregnancy. Science 1976; 194: 948-949.5. Seki K, Uesato T, Tabei T, Kato K. Serum relaxin in patients withhydatidiform mole. Obslet Gyneco11986; 67: 381-383.

Pregnancy without ovarian function A case report

https://www.ajol.info/index.php/samj/article/download/158433/148047

Pregnancy without ovarian function A case report

Abstract

Similar works

Full text

Available Versions

AJOL - African Journals Online