Process for intra-uterine fertilization in mammals and device fo

Surgery – Reproduction and fertilization techniques – Embryo transplantation

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Details

128898, 128899, 6048901, 604 54, 604906, A61B 1743

Patent

active

050840045

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention concerns a fertilisation process for mammals and a device for implementation thereof.


THE KNOWN PRIOR ART

The applicant has previously described a human fertilisation process using a container in patent applications FR-85 16558 and PCT/FR 86 00378.
In this process, ovocytes are removed from a patient in the normal manner, in general using echographic monitoring. The patient initially undergoes ovarian stimulation using Clomid-HMG or LH-RH agonists such as busereline and DTR-P-6.
Follicular liquid is taken into a syringe and immediately examined in the laboratory.
Up to eight ovocytes are then placed in a container constituted by a tube which is open at one end and completely filled with culture medium, for example MENEZZO culture medium B2, containing 10,000 to 20,000 mobile human spermatozoa per milliliter. The tube is then hermetically sealed without the interposition of air, i.e. with no layer of air above the liquid phase.
The sealed tube is then placed in the patient's vaginal cavity for 44 to 50 hours. The tube is then retrieved, opened and the ovocytes are examined in the laboratory.
Fertilised ovocytes which have already started to divide are embryos in their first stages of development.
Up to four of these embryos are then replaced in the patient's uterine cavity using a Frydman catheter.
This CIVETE (intravaginal culture and embryonic transplantation) technique has shown cleavage rates, transfer rates and surgical birth rates at least equal to those obtained using the FIVETE (in vitro fertilisation and embryonic transplantation) technique.
In the CIVETE technique, up to eight ovocytes are placed in a container containing 3.2 ml liquid constituted by medium B2 containing 10,000 to 20,000 mobile spermatozoa per milliliter. The mean volume of liquid per ovocyte is thus 400 microliters, containing 4,000 to 8,000 mobile spermatozoa.
Whilst the CIVETE technique has a number of advantages over the FIVETE technique as it does not require an incubator with an atmosphere of CO.sub.2 -enriched air, there are a few disadvantages. The number of stages of manipulation of male and female gametes is still high and in particular the technique necessitates replacement of one or more embryos in the uterus. Such a number of stages leads to toxicity or even to embryo loss.


SUMMARY OF THE INVENTION

In order to overcome the disadvantages briefly mentioned above the Applicant proposes a process of fertilisation in mammals which is characterised in that it comprises the following steps:
a) providing a container which can be introduced into and lodged in the uterine cavity of the mammal;
b) filling the container with a culture medium, at least one ovocyte of the mammal and spermatozoa;
c) inserting the filled container into the uterine cavity;
d) leaving the container for a specific period of time to allow fertilisation of the ovocyte(s) therein;
e) allowing the contents of the container to escape into the uterine cavity.
This method avoids in particular the final step of embryo transfer from outside the mammal to the interior of the uterine cavity.
According to a preferred feature of the process of the invention, said escape is effected by ejecting the container contents into the back of the uterine cavity in order to increase the chances of implantation of fertilised ovocytes or embryos.
For the same reasons, if the container is of biodegradable-material it is still preferable to insert it towards the back of the uterus.
This process requires a container of a size which is suitable for introduction into and lodging in the uterine cavity of a mammal. It must be much smaller than a container for the FIVETE technique, particularly for human females, as the neck of the human uterus has an opening of only a few millimeters.
The method described above has been developed by the Applicant in work conducted since December 1986 in the form of preliminary studies involving a process comprising the following steps:
1. providing a fine tube having a capacity of about 250 microliter

REFERENCES:
patent: 3910275 (1975-10-01), Babey et al.
patent: 4093708 (1978-06-01), Zaffaroni et al.
patent: 4380997 (1983-04-01), Leibo
patent: 4419986 (1983-12-01), Leibo
patent: 4677967 (1987-07-01), Zarfman
patent: 4701161 (1982-10-01), Lenck
patent: 4790814 (1988-12-01), Fischl et al.
patent: 4865589 (1989-09-01), Simmet et al.
patent: 4902286 (1990-02-01), Ranoux
patent: 4940465 (1990-07-01), Theeuwes et al.
"Human Pregnancy Following Oocyte and Sperm Transfer to the Uterus", The Lancet Ltd., May 8, 1982, by I. Craft et al., pp. 1031-1033.

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