In Vitro Maturation of Oocytes doc

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In Vitro Maturation of Oocytes

Hananel E. G. Holzer, Ri-Cheng Chian, Ezgi Demirtas,

Hanadi Ba-Akdah, and Seang Lin Tan

Department of Obstetrics and Gynecology, McGill University,

Montreal, Canada

INTRODUCTION

Since the first live birth resulting from in vitro fertilization (IVF) was

reported 26 years ago (1), over two million live births have been reported

as a result of IVF. IVF success rates have steadily improved over the years

(2,3) and in many leading IVF centers today, the live-birth rate per cycle in

women younger than 35 years may approach 50% (Table 1). Conventional

IVF treatment requires that the ovaries be stimulated with gonadotropins,

which contain follicle-stimulating hormone (FSH) and luteinizing hormone

(LH), in order to increase the number of mature oocytes retrieved, the num￾ber of embryos available for transfer, and, consequently, to improve preg￾nancy rates. Using controlled ovarian stimulation protocols, the success

rates of IVF treatment have steadily increased and the results of many

leading IVF centers today exceed those of spontaneous conceptions in

healthy, fertile couples (3). However, ovarian stimulation protocols are asso￾ciated with high costs, daily injections of gonadotropins and close monitor￾ing, and carry a considerable risk of causing ovarian hyperstimulation

syndrome (OHSS) (4). Although mild or moderate degrees of OHSS may

not be very dangerous, severe OHSS may be associated with significant

morbidity. Patients with polycystic ovaries (PCO) or polycystic ovarian

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syndrome (PCOS) are particularly prone to develop OHSS with an incidence

of up to 6% (5). The most severe manifestation of OHSS involves massive

ovarian enlargement and multiple cysts, hemoconcentration, and third-space

accumulation of fluid. The syndrome may be complicated by renal failure and

oliguria, hypovolemic shock, thromboembolic episodes, and adult respirato￾ry distress syndrome which, in extreme cases, can even be fatal. Despite many

years of clinical experience, no precise methods have been developed that will

completely prevent severe OHSS after ovarian stimulation (6) and the only

certain method is to avoid stimulating the ovaries with exogenous FSH.

Some patients may also be deterred by the suggested association between

multiple repeated cycles of ovarian stimulation and potential increased inci￾dence of malignant diseases, a worrisome but unproven association (7).

Avoiding ovarian stimulation and collection of immature oocytes would

eliminate the risk of OHSS. Indeed, research on immature oocytes and their

maturation was conducted as early as the mid-1930s (8).

OOCYTE MATURATION IN VIVO AND IN VITRO

Follicle Development and Oocyte Maturation In Vivo

The development of human oocytes is arrested at the prophase I stage of

meiosis during fetal life. At birth, there are approximately one million pri￾mordial follicles in the ovaries (9), each of which consists of an oocyte

surrounded by a few flattened pregranulosa cells enclosed by a basement

Table 1 Results of Fresh In Vitro Fertilization (IVF) Cycles Including IVF and

IVF-Intracytoplasmic Sperm Injection Excluding Oocyte Donation Cycles

Age group <35 35–37 38–40

Cycles started (% of total) 150 (33.6) 123 (27.6) 110 (24.7)

Cycles cancelled 6 6 2

Oocytes collected (mean) 14.4 14.0 12.0

Embryos transferred (mean) 2.6 2.9 3.3

Pregnancy rate per cycle started (%) 60.0 48.8 41.8

Pregnancy rate per embryo transfer (%) 65.7 53.1 45.1

Implantation rate per embryo (%) 36.6 24.5 15.1

Live birth rate per started cycle (%) 46.0 33.3 25.5

Live birth rate per embryo transfer (%) 50.4 36.3 27.5

Number of babies born 94 57 36

Singletons 46 25 22

Twins 21 16 7

Triplets 2 0 0

Source: McGill Reproductive Center.

128 Holzer et al.