Assisted Fertilization potx

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Assisted Fertilization

Andre´ Van Steirteghem

Centre for Reproductive Medicine, Academisch Ziekenhuis, Vrije Universiteit

Brussel, Brussels, Belgium

INTRODUCTION

Since the birth of Louise Brown, the first test tube baby, in 1978 (1), in vitro

fertilization (IVF) has become a well-established treatment procedure for

certain types of infertility—including long-standing infertility due to tubal

disease, endometriosis, unexplained infertility, or infertility involving a male

factor. However, it became obvious that certain couples with severe

male-factor infertility could not be helped by conventional IVF. Extremely

low sperm counts, impaired motility, and poor morphology represent the

main causes of failed fertilization in conventional IVF. To tackle this prob￾lem, several procedures of assisted fertilization based on micromanipulation

of oocytes and spermatozoa have been established. These strategies have

culminated in intracytoplasmic sperm injection (ICSI), where a single sper￾matozoon is directly injected into the ooplasma. In 1992, our group reported

the first human pregnancies and births after replacement of embryos gener￾ated by this novel procedure of assisted fertilization (2). Since then, the

number of worldwide centers offering ICSI has increased tremendously,

as has the number of treatment cycles per year (3). Because of the wide￾spread application of ICSI as the ultimate and only option for successful

treatment of severe male infertility due to impaired testicular function or

obstruction of the excretory ducts, concern about its efficacy and safety

is appropriate.

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This chapter surveys the current status of ICSI, emphasizing patient

selection for ICSI, gamete handling prior to microinjection, the ICSI pro￾cedure and outcome parameters of fertilization, and embryo cleavage after

ICSI. Furthermore, outcome and children’s health after IVF and ICSI will

be summarized including pregnancy complications, major malformations,

and possible causes of adverse outcome.

INTRACYTOPLASMIC SPERM INJECTION

History of ICSI

Extremely low sperm counts, impaired motility, and abnormal morphology

represent the main causes of failed fertilization in conventional IVF. Today,

ICSI is the ultimate option to treat these cases of severe male-factor infer￾tility. One single viable spermatozoon, preferably of good morphology, is

selected by the embryologist and injected in each oocyte available.

ICSI is based on micromanipulation of oocytes and spermatozoa.

Initially, partial zona dissection (PZD) was established to facilitate sperm

penetration (4–7). The barrier to fertilization represented by the zona pellu￾cida was disrupted mechanically so that the inseminated sperm cells

obtained direct access to the perivitelline space of the oocyte. Subzonal

insemination (SUZI) represented the next step in micromanipulation tech￾niques (8–11). SUZI enabled the immediate delivery of several motile sperm

cells into the perivitelline space by means of an injection pipette. ICSI is

even more invasive because a single spermatozoon is directly injected into

the ooplasma, thereby crossing not only the zona pellucida but also the

oolemma. ICSI had been first used successfully to obtain live offspring in

rabbits and cattle (12), and a preclinical evaluation was reported by the

Norfolk group (13). The first human pregnancies and births resulting from

this novel assisted-fertilization procedure were reported in 1992 (2). There￾after, ICSI was revealed to be superior to SUZI in terms of oocyte fertilization

rate (14–17), number of embryos produced, and embryo implantation rate

(14–17). As a result, ICSI has been used successfully worldwide to treat infer￾tility due to severe oligo-astheno-teratozoospermia, or azoospermia caused

by impaired testicular function or obstructed excretory ducts (18,19).

Since the first publication describing the ICSI procedure, minor

modifications contributed to reduced rates of oocyte degeneration, oocyte

activation (one-pronuclear), and abnormal fertilization (three-pronuclear).

Hyaluronidase may be responsible for oocyte activation; therefore, the con￾centration used during oocyte denudation and the exposure time of oocytes

to the enzyme have been reduced (20). The moment of denudation relative to

oocyte pick-up (immediately or four hours later) does not influence the ICSI

results (21). The orientation of the polar body during injection does, how￾ever, influence embryo quality (22). Motile sperm cells are selected and

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