J. Cohen

Sequential use of clomiphene citrate, human menopausal gonadotropin, and human chorionic gonadotropin in human in vitro fertilization. II. Study of luteal phase adequacy following aspiration of the preovulatory follicles*

The 88 patients included in the in vitro fertilization program during 113 cycles were submitted to superovulation by sequential use of clomiphene citrate, human menopausal gonadotropin, and human chorionic gonadotropin. No correlation was found between estradiol and progesterone levels during the luteal phase and estradiol on the days preceding administration of human chorionic gonadotropin. Nineteen biopsies of the endometrium were carried out. The importance of the increase of estradiol between the day before and the day of administration of human chorionic gonadotropin is positively correlated with the quality of the endometrium.

Ultrastructure of the human preovulatory oocyte

The ultrastructure of preovulatory human oocyte—cumulus complexes was described after inducing maturation by clomiphene, human menopousal gonadotropin (hMG), human chorionic gonadotropin (hCG) treatment. The majority of the oocytes was at metaphase, II of meiosis, with a radially orientated spindle. The oocyte surface was covered by a multitude of microvilli. Cortical granules were nonuniformly distributed along the cortex. A cytoplasmic polarization was observed. The cytoplasmic organelles were in general uniformly dispersed, with the exception of a narrow segment within which cytoplasmic membranes and mitochondria formed clusters. The spirndle was usually found at the borderline between the two regions of the cytoplasm. The functional significance of this polarization is not yet known.

Transvaginal sonographically controlled ovarian puncture for oocyte retrieval for in vitro fertilization

Two hundred twenty-two patients took part in a trial of follicle puncture via the transvaginal route under sonographic control for the purpose of in vitro fertilization (IVF). Induction protocols were mainly human menopausal gonadotropin (hMG)+human chorionic gonadotropin (hCG) and clomiphene + hMC + hCG. In 79.7% oocyte aspiration could be achieved without difficulty via the transvaginal route. An average number of 4.7 oocytes per attempt was obtained: 10.7% evolutive pregnancies were obtained. No major incident was noted. This technique offers several crucial advantages: it reduces surgical risk, reduces the length of the patients stay in hospital as well as the overall cost of the procedure, and it also makes possible puncture in some cases hitherto regarded as excluded.

The future of international registries for assisted reproductive technologies

In 1991, national registers were practically nonexistent, and each country could compare the quality of its results only within the country itself—not to the results of other nations. Jacques Testart and Jacques de Mouzon participated actively in the first document that was released to each participant of the meeting; this document concerned AMP for the year 1989. Among the 40 countries or groups of countries that were requested to send data, 24 produced an effective contribution—some via previous surveys, others via personal answers from national correspondents acting for their countries.

Morphologic and Cytologic Study of Human Embryos Obtained by In Vitro Fertilization

Among the main reasons for implantation failure of human embryos obtained by IVF, the embryo viability is the most difficult parameter to analyse. Indeed, as embryos are replaced at the two- or four-cell stage, nothing is known about their developmental capacity. For this purpose, we investigated the morphologic and cytologic aspects of the embryos obtained during the last year.

Gender selection: is there a European view?

There is no European view on gender selection. Conclusions of the ESHRE Ethics Task force are reported.

The Implantation Window in Humans after Fresh or Frozen-Thawed Embryo Transfers

In mammals, the opdmum time for embryo transfer greatly depends upon the species. In rodents, a high synchrony between the donor and the recipient is required.1,2 In sheep3 and catde4 too, better results are obtained with synchronous transfers. In other species, such as pigs5, mares6 and monkeys7, an asynchrony up to one or even two days is possible.

Regulations for preimplantation genetic diagnosis in France.

A commentary on regulations for PGD in France.

A function test to assess the responsibility of oocyte and sperm quality in in vitro fertilization failure.

It is obvious that both oocyte and sperm quality play a major role in the success of in vitro fertilization (IVF). In the case of total fertilization failure (TFF), and mainly for idiopathic infertility, it is often difficult to attribute the failure to either sperm or oocyte accurately. Indeed, oocyte quality is a parameter very difficult to appraise. A few criteria can easily be taken into account noninvasively, i.e., cumulus cell dispersal, nuclear maturity assessed by the presence of the first polar body at the time of insemination, absence of any sign of atresia, and sperm-zona pellucida binding, the day after insemination (1). When observing oocytes by transmission electron microscopy, abnormalities were sometimes evident in the cytoplasm of mature oocytes, such as delayed formation of aggregates of the smooth endoplasmic reticulum, demonstrating some degree of asynchrony between nuclear and cytoplasmic maturation and showing that nuclear maturation is not a sufficient criterion to appraise the capacity of oocytes to be fertilized (2). Certain characteristics of the follicular fluid biochemistry such as al-antitrypsin, proteoglycan, and immunoglobulin levels can also reflect differences in oocyte maturity and fertilizability (3). Moreover, a comparison of the basal secretion of steroids (progesterone, testosterone, and estradiol) in cumulus cells of different types of cumulus--oocyte complexes confirmed that oocytes recovered after a stimulation treatment consist of a heterogeneous population, and in fact they differ in their potential for fertilization and consequent cleavage (4). If we are at a loss when facing the problem of oocyte quality, the situation is even worse and more complex in the case of sperm quality. There is now a consensus on the fact that spermiocytograms do not predict sperm potential. Indeed, we occasionally obtained fertilizations with no more than 500,000 motile sperm/ml in the ejaculate. A battery of tests, such as the sperm penetration assay (SPA) (5), the hypoosmotic sperm swelling test (6), and the hemizona assay (7), have all shown various degree of correlation with oocyte fertilizability. The most widely applied test in clinical practice, i.e., the sperm penetration assay, has an advantage compared to biochemical assays: it gives information about physiologically functional acrosome reactions and sperm fusiogenic properties, prerequisite for fertilization. It is, however, time-consuming and costly, requiring the maintenance of an animal breeding unit and a special laboratory with trained staff. Sperm penetrat ion assays using human oocytes that failed to fertilize in vitro were developed recently as an alternative to SPA. Either saltstored (8), intact (9,10), zona-free (9-11), or cryopreserved (12), these oocytes seem to provide an accurate system to assess sperm function and fertilizing potential. We report here on a test developed to appraise the respective roles of oocyte and sperm quality after fertilization failure in couples with either idiopathic or male infertility, by reinseminating unfertilized eggs with sperm from a fertile donor.

The French Bioethic Law, July 29, 1994

ConclusionsThis law is still incomplete because the application rules are not yet published and may modify the first interpretations.Actually, the law brings some good points:authorization of ART,permittance of embryo freezing, andanonymity of the dondation. But there are many contradictions and ambiguities:contradiction between the “respect of the human being” as soon as life begins and the legal abortion law (until 12 weeks),ambiguities concerning the research on embryos (What is “integrity” of the embryo) and ambiguities on the statis of the embryo after the death of the father (it can only be given to another couple), andambiguity and difficulty concerning the intervention of a legal authority (judge or lawyer). This law, in my opinion, reflects the uncertainty of the deputies and senators and the pressure of the Catholic Church.At any rate, the doctor who does not apply the law faces 10 years of inability to practice medicine and heavy fining. All condemnations are very severe. The law may be revised in 5 years from 1994.