The earliest stages of development in most animals, including the few mammalian species that have been investigated, are regulated by maternally inherited information. Dependence on expression of the embryonic genome cannot be detected until the mid two-cell stage in the mouse, the four-cell stage in the pig (J. Osborn & C. Polge, personal communication), and the eight-cell stage in the sheep. Information about the timing of activation of the embryonic genome in the human is of relevance not only to the therapeutic practice of in vitro fertilization and embryo transfer (IVF), but more importantly for the successful development of techniques for the preimplantation diagnosis of certain inherited genetic diseases. We describe here changes in the pattern of polypeptides synthesized during the pre-implantation stages of human development, and demonstrate that some of the major qualitative changes which occur between the four- and eight-cell stages are dependent on transcription. In addition, it appears that cleavage is not sensitive to transcriptional inhibition until after the four-cell stage.

Human gene expression first occurs between the four- and eight-cell stages of preimplantation development

La presente revue considere les donnees recentes concernant les produits impliques dans l'activation du genome de l'embryon chez plusieurs especes

https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.1080260113

Transition from maternal to embryonic control in early mammalian development: a comparison of several species.

Uterine malformations consist of a group of miscellaneous congenital anomalies of the female genital system. Their mean prevalence in the general population and in the population of fertile women is approximately 4.3%, in infertile patients approximately 3.5% and in patients with recurrent pregnancy losses approximately 13%. Septate uterus is the commonest uterine anomaly with a mean incidence of approximately 35% followed by bicornuate uterus (approximately 25%) and arcuate uterus (approximately 20%). It seems that malformed uterus and especially septate uterus is not an infertility factor in itself. However, it may have a part in the delayed natural conception of women with mainly secondary infertility. On the other hand, patients with uterine malformations seem to have an impaired pregnancy outcome even as early as their first pregnancy. Overall term delivery rates in patients with untreated uterine malformations are only approximately 50% and obstetric complications are more frequent. Unicornuate and didelphys uterus have term delivery rates of approximately 45%, and the pregnancy outcome of patients with untreated bicornuate and septate uterus is also poor with term delivery rates of only approximately 40%. Arcuate uterus is associated with a slightly better but still impaired pregnancy outcome with term delivery rates of approximately 65%. Women who have undergone hysteroscopic septum resection and have been reported in the different series comprise a highly selected group of symptomatic patients with term delivery and live birth rates of only approximately 5%. Hysteroscopic treatment seems to restore an almost normal prognosis for the outcome of their pregnancies with term delivery rates of approximately 75% and live birth rates of approximately 85%. It seems, therefore, that hysteroscopic septum resection can be applied as a therapeutic procedure in cases of symptomatic patients but also as a prophylactic procedure in asymptomatic patients in order to improve their chances for a successful delivery.

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Clinical implications of uterine malformations and hysteroscopic treatment results

Even when conditions are optimal, the maximum chance of a clinically recognized pregnancy occurring in a given menstrual cycle is 30-40%. Increasing evidence points to preclinical pregnancy loss rather than failure of conception as the principal cause for the relatively low fecundity observed in humans. While sensitive assays for hCG have provided a glimpse of the events occurring between implantation and the missed menstrual period, new cytogenetic techniques have further opened this 'black box', providing novel insights into the causes of early pregnancy wastage. In this article, the evidence and causes of preclinical or 'occult' pregnancy are reviewed, and the implications for the infertile patient are addressed.

Conception to ongoing pregnancy: the ‘black box’ of early pregnancy loss

Ovarian hyperstimulation syndrome (OHSS) is a rare iatrogenic complication of ovarian stimulation occurring during the luteal phase or during early pregnancy. Fortunately, the reported prevalence of the severe form of OHSS is small, ranging from 0.5 to 5%. Nevertheless, as this is an iatrogenic complication of a non-vital treatment with a potentially fatal outcome, the syndrome remains a serious problem for specialists dealing with infertility. The aim of this literature review was to determine whether it is possible to identify patients at risk, and which preventive method should be applied when an exaggerated ovarian response occurs. Data pertaining to the epidemiology and prevention of OHSS in women were searched using Medline, Current Contents and PubMed, and are summarized. Preventive strategies attempt either to limit the dose or concentration of hCG or to find a way to induce luteolysis without inducing a detrimental effect on endometrial and oocyte quality. The following particular preventive strategies were reviewed: cancelling the cycle; coasting; early unilateral ovarian follicular aspiration (EUFA); modifying the methods of ovulation triggering; administration of glucocorticoids, macromolecules and progesterone; cryopreservation of all embryos; and electrocautery or laser vaporization of one or both ovaries.

/pdf/epidemiology-and-prevention-of-ovarian-hyperstimulation-2sp2m8oeef.pdf

Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review

The success rate of human embryo cryopreservation depends on technical and embryonic parameters. First of all, the cryoprotectant can affect embryo survival as we found by comparing two freeze-thaw procedures using propanediol (PROH) (1.5 mol) alone or with sucrose (0.1 mol). Embryo survival was significantly enhanced with sucrose (62 versus 32%). Embryo quality is another major parameter involved in the success of freezing; the rates of positive survival were found to be 67% for morphologically normal embryos versus 49% for embryos with fragments (P less than 0.001). The efficiency of embryo cryopreservation in an IVF programme could be estimated in 1986: a woman with extra embryos, stored after transfer of 3-4 fresh embryos (16% of all cycles), can expect a 22% pregnancy rate per transfer of fresh embryos and a 32% pregnancy rate per collection after transfer of the stored eggs. A comparative study of the cryopreservability of immature or mature oocytes was performed in humans. Human oocytes have a low survival rate (36%) whatever the cryopreservation protocol or the initial maturation stage. Immature human oocytes could survive freezing and thawing, mature and be fertilized in vitro, but with a very low efficiency.

Cryopreservation of human embryos and oocytes

A cytogenetical analysis was performed on 151 unfertilized oocytes, 22 fertilized eggs at the pronuclear stage, and 108 cleaved embryos obtained in the course of in vitro fertilization (IVF). Thirty-two per cent of unfertilized oocytes were abnormal, carrying nullisomies or disomies, mainly of D and G chromosomes, and a structural anomaly (Gq-) in one case. Fertilized eggs showed frequent asynchronism in the development of pronuclei and only 2 out of 8 karyotyped pronuclei were normal. Cleaved embryos were classified according to the number of pronuclei observed 17 hours after insemination. One per cent displayed a single pronucleus, and haploid chromosome complements were found in the corresponding cleaved embryos which were considered to be parthenotes. The rate of chromosome abnormalities of diploid eggs depended on their morphological aspect. Healthy cleaved embryos carried 12.5% of anomalies while this rate reached 37% in fragmented embryos (p less than 0.05). Lastly, 6% of fertilized eggs displayed three pronuclei or more. Only 41% of the corresponding embryos were triploid. Diploidy or diploidtriploid mosaicism were often encountered. This leads to a 21% rate of abnormalities in the preimplantation embryos. Parental karyotyping and HLA typing were carried out in a series of eight couples with in vitro idiopathic infertility or recurrent embryo degeneration in vitro. No abnormality was noted. According to these results, a model of natural selection of normal conceptuses is proposed.

From oocyte to embryo: a model, deduced from in vitro fertilization, for natural selection against chromosome abnormalities.

Between February 1987 and February 1989, 13 women with primary ovarian failure due to gonadal dysgenesis were treated with embryo transfer following ovum donation in 22 cycles. Eight pregnancies were obtained (36.7% per transfer); four births of normal children, two spontaneous abortions and two other pregnancies currently ongoing (between 5 and 8 months). An association of percutaneous oestradiol, oestradiol valenate and intravaginal progesterone was used as hormone substitution and embryo transfer was only performed following assessment of the endometrium during a previous cycle. Apart from the day of embryo transfer, which was the same for all patients (the 2nd day after initiation of progesterone) various prognostic factors were analysed. These were the type of gonadal dysgenesis (45 XO, 46 XX or 46 XY), the number of embryos replaced, whether they had been frozen, whether the egg donor was anonymous and finally the influence of the hormone substitution protocol. Only the number of embryos replaced and the substitution protocol seemed to influence the implantation rate. The other parameters, and in particular the type of gonadal dysgenesis, seemed to have no effect on the results. The pregnancy rate per transfer was 30% for 45 XO (10 transfers), 25% for 46 XX (eight transfers) and 75% for 46 XY (four transfers).

Pregnancies following ovum donation in gonadal dysgenesis

Freezing and thawing (F - T) was applied to 490 early human embryos using propanediol as cryoprotectant The survival rate of embryos frozen with propanediol alone did not exceed 31% (26/83) The combination of propanediol and sucrose, however, significantly increased the percentage of surviving (248/407 = 61%) and intact (188/407 = 46%) embryos and seemed to enhance embryo viability as suggested by the implantation rate (145 versus 8%) without, however, any statistical significance Embryo survival, but not viability, was correlated with morphological features, whereas neither the age of embryos (1, 2 or 3 days post-insemination) nor the segmentation stage (regular or intermediate) were involved in F - T ability Thirty-eight F - T embryos implanted when replaced in utero, representing 8% of all F - T embryos and 14% of the F - T replaced embryos The pregnancy rate per transfer reached 19% (35/185) and was identical to the pregnancy rate per transfer of fresh embryos (253/1149 = 22%) In oocyte donation, too, embryo freezing did not impair the pregnancy rate (25%) In spontaneous cycles, synchronous transfer gave better results than asynchronous transfers (20 versus 10%), but spontaneous cycles had no significant advantage (16% pregnancy/transfer) as compared to stimulated (26%) and artificial (27%) cycles

M. Plachot

Papers

Cryopreservation of human embryos and oocytes

From oocyte to embryo: a model, deduced from in vitro fertilization, for natural selection against chromosome abnormalities.

Pregnancies following ovum donation in gonadal dysgenesis

Human embryo cryopreservation, extrinsic and intrinsic parameters of success

Nucleologenesis in the human embryo developing in vitro: ultrastructural and autoradiographic analysis