In vitro maturation of human oocytes with subsequent IVF or ICSI . An observational study with follow up of the children.

In the menstrual cycle a cohort of early antral follicles is present at the
onset of the follicular phase. A few of these early antral follicles are
recruited for further growth and development. However only one will become the
dominant follicle, resulting in atresia of the others.
During IVF-treatment women are stimulated by subcutaneous injections with
supraphysiological doses of FSH, often combined with downregulation of the
spontaneous natural cycle with GnRH analogue (COH, controlled ovarian
hyperstimulation). This overrules the natural dominancy selection and leads to
support of the complete recruited cohort, resulting in ideally 8-15 follicles.
The oocytes are then picked up form these follicles by transvaginal ovum
pick-up and most oocytes are in the metaphase II stage. Subsequently IVF or
ICSI can be performed.
Disadvantages of COH are the physical impact on the patient as well as the risk
of ovarian hyperstimulation syndrome (OHSS). In severe cases (0,5-5% of all IVF
cycli) this forms a potential lifethreathening complication. Especially
patients diagnosed with polycystic ovarian syndrome (PCOS) have an increased
risk for developping OHSS (Delvigne and Rozenberg, 2002).
An alternative for conventional IVF with COH is in vitro maturation (IVM). In
this approach none or only minimal stimulation with FSH is applied. Ovum
pick-up takes place in the early antral phase and only immature (metaphase I)
oocytes are harvested. These oocytes are transferred to IVM culture medium and
mature in vitro to the metaphase II stage within 24-36 hours. Subsequently
these matured oocytes are use for IVF or ICSI in the same way as in
conventional IVF with COH.
The main advantage of IVM is the absence of COH and therefore the risk for OHSS
is abolished. Furthermore this procedure is especially useful for PCOS patienst
as they have more early antral oocytes present due to their PCOS.

The objective of this observational study is the safe introduction of clinical
applied IVM in The Netherlands. During this study, the number and quality of
the oocytes and embryos will be studied as well as pregnancy development.
Emphasis will be on the long term development of the children born after this
IVM procedure. Shortly after birth, at 6 months, 1-, 2- and 5-years of age
mental and motoric development will be scored according to national and
international standards.

This is an observational study with the following design.
Patients will be informed extensively before they will participate in this
study. Participation will only take place after written informed consent by the
patients.
The menstrual cycle of the patient will be monitored endocrinologically as well
as by ultrasound. The appearance of a dominant follicle in combination with an
increase of the endometrium thickness to 5 mm determines an appointment for
ovum pick-up the following day. Ovum pick-up will be performed transvaginal
under ultrasound guidance and local anaesthesia with lidocain or intravenous
fentanyl as is routinely used in our clinic. The oocytes are collected by a
laboratory technician using an (veterinary) Embryo Collector (steel mesh) and
transferred to IVM culture medium. Culture for 30 hours in this medium leads to
final oocyte maturation and the matured oocytes are used for IVF or ICSI.

The main advantage of IVM is the absence of COH and therefore the risk for OHSS
is abolished.