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Preimplantation genetic testing-human leukocyte antigen '(PGT-HLA) only' refers to the HLA typing of single or few cells biopsied from in vitro fertilized preimplantation embryos. The aim of the procedure is to establish a pregnancy, in which the fetus is HLA compatible with an affected sibling in need of a hematopoietic stem cell transplantation (HSCT). During PGT-M-HLA, the identification of a HLA-compatible embryo is combined with the detection of mutation(s) underlying immunodeficiencies and hemoglobinopathies. We report a combined retrospective and prospective cohort analysis of PGT-(M-)HLA procedures carried out from 1998 until 2017, with follow-up of transplantations to 2019. During the study period, 234 couples from 22 countries were invited for a multidisciplinary consultation. Two couples were rejected and 70 couples declined (various reasons), leaving 162 couples for which 414 clinical cycles were carried out. Cleavage stage biopsy followed by single-cell multiplex PCR for short tandem repeat-based haplotyping was applied in most cases (98.7%). The diagnostic efficiency was high (94.8%) but only 16.5% of the embryos was genetically suitable for transfer. Fresh and frozen-thawed embryo transfer resulted in 67 clinical pregnancies, 63 deliveries, and 74 live births, of which 60 children were HLA compatible. This yielded a live birth delivery rate of 30.3% per transfer. Information on neonatal characteristics of the matching PGT-(M-)HLA children showed reassuring outcomes. So far, HSCT was carried out successfully for 25 out of 26 cases. In conclusion, our data show that PGT-(M-)HLA is a valuable procedure: the high complexity and limited delivery rate are balanced by the successful HSCT outcome and the positive impact on families.

A 21-year-old primigravida underwent caesarean section at term for failure-to-progress beyond 9 cm. The uterus was exteriorised and a right-sided lateral extension of the uterine incision was repai...

Hypophosphatasia is a rare inherited disorder characterized by defective bone mineralization and deficiency of serum and tissue liver/bone/kidney tissue alkaline phosphatase (L/B/K ALP) activity. We report here the characterization of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutations in a series of 11 families affected by various forms of hypophosphatasia. Nineteen distinct mutations were found, 7 of which were previously reported. Eleven of the 12 new mutations were missense mutations (Y11C, A34V, R54H, R135H, N194D, G203V, E218G, D277Y, F310G, A382S, V406A), the last one (998-1GT) was a mutation affecting acceptor splice site.

The study aimed to estimate the proportion of unplanned pregnancies among mothers delivering at the referral Harare Hospital and to describe their levels of contraceptive use and awareness in relation to the planning of pregnancy.Systematic sample of mothers who had just delivered identified through maternity delivery, records. The study was analysed as a case-referent study where cases where mothers who had unintended pregnancies and those with intended or planned pregnancies served as referents.Postnatal wards of Harare Maternity Hospital.923 mothers following delivery.Socio-demographic characteristics, pregnancy planning, contraceptive history and contraceptive knowledge.Of the 923 deliveries studied, 377 (41%) were unintended (cases), of which 9% were unwanted. Mothers aged 19 years or below (Odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.6 to 3.7) and those aged 35 years or above (OR = 3.2, 95% CI = 1.8 to 5.5) were significantly more likely to report the index pregnancy as having been unintended. Nulliparous (OR = 2.4) and parity five or more (OR = 8.2) mothers were at significantly increased risk of unintended pregnancy. Mothers presenting with unintended pregnancies were also significantly more likely to be single (OR = 7.8), divorced/separated or widowed (OR = 6.0). Contraceptive ever use was 53% and 58% in cases and referents, respectively. The combined oral contraceptive pill was the most commonly known and used method of contraception. Contraceptive failure was reported by 23% of mothers with unplanned pregnancies. Previous use of the progesterone only pill (OR = 2.2), the condom (OR = 2.3) or the IUCD (OR = 6.3) were significantly associated with the likelihood of reporting with unplanned pregnancy. Mothers in both groups were concerned about contraceptive method failure, irregular menstruation and perceived subsequent infertility with contraception. Failure to discuss family planning with the male partner (OR = 2.3) or partner refusing use of contraception (OR = 2.8) constituted risk factors for unplanned pregnancy.Results point to the need for wider contraceptive counselling and provisions which encourage and involve the male partner. Programmes for reproductive health services and education should target women in identified high risk circumstances.

To explain the U-shaped curve of stillbirth rates (SBR) in Harare.A retrospective descriptive study.Greater Harare Maternity UnitA 15pc (approx.) sample of deliveries recorded in Labour Ward registers in 1979, 1984 and 1989.Stillbirth or livebirth.Some changes over the three years (e.g. proportion of primipara) indicate that obstetric "riskiness" of the population changed in a way which could explain the changes in SBR.However SBR's of large babies (birth weight 2,500 g to 4,499 g) increased and decreased over the years implying that changes in quality of care may also have contributed to the changes in SBR.The perinatal mortality rate at Zimbabwe's Greater Harare Maternity Unit has demonstrated a "U"-shaped curve since independence, from 40/1000 total births in 1980 to 35/1000 in 1984 and 50/1000 in 1991. To determine whether this trend reflects changes in the quality of perinatal care or changes in the obstetric risk level of the population, a retrospective review was conducted of a 15% sample of deliveries at the maternity unit and all 10 Harare City Maternity Clinics in 1979 (3431 cases), 1984 (4913 cases), and 1989 (4567 cases). The perinatal mortality rates for these years were 40, 34, and 47/1000 live births, respectively. The stillbirth rates were 32, 26, and 32/1000, respectively. For large babies (2500-4499 gm birth weight), these rates were 12.3, 9.2, and 13.4/1000, respectively. Maternal age remained unchanged in the 3 periods; however, there were significantly fewer primiparae and multiple births in 1984. The study was limited by a lack of data in the records on risk factors such as human immunodeficiency virus and social class. The changes in outcome for large babies implies that the quality of perinatal care improved until 1984, then declined.

The authors studied 38 cases of benign forms of MS, defined as those allowing a normal or nearly normal social, occupational, and family life over a "long" period of tens of years, for at least 15 years (mean : 28 years, range : 15 to 68 years).--Forms with rare relapses with long intervals between them (18 cases), and a mean period of 14 years (5 to 30) between the first and second episode.--Recurrent forms (17 cases) with frequent attacks (one or two a year), including 8 cases with no further relapses after an average period of 10 years, and 9 cases with continuation at the same rhythm for 15 to 23 years.--Secondarily progressive forms belonging to both types--8 in the first and 3 in the second--characterized by the late onset (mean : 25 years, range : 15 to 47 years) of a progressive paraplegia.--Slow forms (3 cases) with an early but only slowly evolving progressive phase, which fall into a border line category of benign forms. Independently of the mean age of onset (26 years); the predominence of females (2.2); and the symptomatology of the first attack (40 p. 100 involve the cranial nerves, and 40 p. 100 have pyramidal signs), the two essential characteristics of benign forms are the remarkable regression of relapses (rare of frequent) and the absence of a progressive phase. Once the 10-year point has been passed without permanent disability the prognosis is good, but with the reserve that the disease can become worse at a later stage.

Three cases of the disease are reported by the author. Clinical observations showed them to be unilateral lesions, not affecting the Vth motor nerve fibers, and without any other neurological disorder. The lesions had been present for 16, 8, and 2 years respectively. Radiography and tomography of the petrous bone was normal, as was tomodensitometry in the third case. The three patient developed a syndrome with dysesthesia and hypoesthesia after several weeks or months, and this remained fairly constant. In such cases which progress over a long period of time, in which there is no anatomical basis, and in which no aetiology can be found, the only conclusions to be drawn are clinical ones: that this is a true syndrome of chronic isolated sensory neuropathy of the trigeminal nerve.

The case is described of a woman of 26 suffering (like her mother, a brother and a sister) from a progressively degenerating cerebellar syndrome, at first considered to be hereditary cerebellar ataxia, but which, after action myoclonus appeared, was diagnosed as dyssynergia cerebellaris myoclonica (D.C.M.). Anatomical verification however revealed a syndrome of olivo-ponto-cerebellar atrophy comprising massive demyelinisation of the white matter of the cerebellum and of the cerebellopontine fibres; atrophy of the pontine nuclei; the cerebellar cortex itself was severely affected; moderate nigral lesions; marked spinal lesions of the cerebellospinal fasciculi and of the posterior columns; lesions of the anterior horns and of the bulbar nuclei; cortical chromatolysis. The fact that the dentate system remained unaffected, also noted in some cases of olivo-ponto-cerebellar atrophy with myoclonus, whilst in a number of other cases the lesion remains clinically silent, emphasises the difficulty in establishing an accurate correlation between myoclonus and dentate nucleus. Discussion of the nosological limits of D.C.M.: confirmed cases generally displayed lesions of the dentate system and hereditary degenerative spino-cerebellar lesions. The same clinical symptoms can be observed in cases which do not come under this classification--or even under that of degenerative conditions of the cerebellar system--and D.C.M. appears to be only a syndrome, the Ramsay-Hunt syndrome.