Ovulation Stimulation with Gonadotropins

182 Pages·2015·5.19 MB·English

by  Jean-Claude Emperaire (auth.)

Ovulation
Stimulation with
Gonadotropins
Jean-Claude Emperaire
Foreword by
Bruno Lunenfeld
123
Ovulation Stimulation with Gonadotropins

Jean-Claude Emperaire
Ovulation Stimulation
with Gonadotropins
Foreword by Bruno Lunenfeld
Jean-Claude Emperaire
Bordeaux
France
This work is a translation from the book: Emperaire J.C., Pratique de la stimulation ovulatoire
par les gonadotrophines, Springer-Verlag France, ISBN: 978-2-8178-0397-5, 2013
ISBN 978-3-319-18653-5 ISBN 978-3-319-18654-2 (eBook)
DOI 10.1007/978-3-319-18654-2
Library of Congress Control Number: 2015947362
Springer Cham Heidelberg New York Dordrecht London
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To my beloved wife Cosette and sons
Pierre and Julien

Foreword
G onadotropin therapy is so central to infertility treatment that it is easy to overlook
the considerable discovery and research that preceded our understanding of the
reproductive process, diagnostic procedures, treatment protocols, and the produc-
tion of the effective and safe therapeutic agents available today.
The history underpinning this development spans over 300 years and provides a
splendid example of how basic animal experimentation and technological advances
have progressed to clinical application.
F ollowing the discovery of germ cells in 1677, and the realization that fertiliza-
tion involved the merging of two cell nuclei, one from the egg and one from sperm,
in 1870, it took another 40 years to discover the interplay between the hypothala-
mus, pituitary, and gonads in 1910.
The gonadotropins were discovered in 1927. Gonadotropins, such as pregnant
mare serum gonadotropin (PMSG), were fi rst introduced for ovarian stimulation in
1930. However, the use of PMSG led to antibody formation and had to be with-
drawn. Following our discovery that urinary menopausal gonadotropins (HMG)
could stimulate gonadal function in 1953, and the delivery of the fi rst child by our
group in 1961, the path opened to controlled ovarian stimulation. Human pituitary
gonadotropins extracted from pituitaries of cadavers (HPG) produced good results,
but its use came to an end in the late 1980s when it was linked to the development
of Creutzfeldt-Jakob disease.
With the availability of HMG, clomiphene citrate, ergot derivatives, GnRH ago-
nists and antagonists, as well as metformin, algorithms were developed and have
been used successfully to treat infertility for the past four decades.
Following Heape’s fi rst rabbit embryo transfers in 1880, Pincus’ attempts at IVF
in rabbits in 1934, Menkin and Rock’s in vitro fertilization of human eggs in 1944,
and Chang’s rabbit birth following IVF, the fi rst human IVF baby was born from a
natural cycle in 1978.
F ollowing the fi rst IVF baby born after gonadotropin stimulation in 1981, IVF
procedures became standard practice for the management of tubal factor infertility
and increased the demand of gonadotropins signifi cantly. The demand was further
increased after donor embryo and donor egg transfer technology permitted treating
women with ovarian failure, and intracytoplasmic injection of a single spermato-
zoon into an oocyte opened the way to treat male infertility.
vii
viii Foreword
The main agents for controlled ovarian stimulation for IVF were gonadotropins
and GnRH analogues, and it soon became evident that there would never be a suf-
fi cient urine supply to cover the increasing world demand for gonadotropins.
Recombinant DNA technology now allows the production of pharmacologically
active pure FSH, LH, and hCG preparations in unlimited quantities, minimizing any
potential risk of disease transmission via biological contamination. The introduc-
tion of recombinant gonadotropins with more than 99 % purity gradually replaced
HMG preparations worldwide.
W ith batch to batch consistency of gonadotropin preparations, methods could be
developed to predict and select the correct dose and the optimal protocol for each
patient. In 2012 it was calculated that assisted reproductive technology with the use
of gonadotropins for ovulation induction has helped couples deliver more than 12
million children: 7 million after ovulation induction or intrauterine insemination
and another 5 million through in vitro fertilization.
H owever, examination of worldwide results reveals still wide variations in live
birth rates. This situation could be changed if women would seek treatment before
the age of 35, if clinicians would use optimal protocols to diagnose and manage
their patients, and if embryologists would use the best tools to select the best
embryo. All this we can learn from this small but precise volume.
A s a highly experienced and well-recognized specialist, Dr. Jean-Claude
Emperaire describes the correct use of these protocols in a very didactic and scien-
tifi c manner in this book. This volume will help clinicians to a better understanding
of the physiology of reproduction, the therapeutic agents they use, and the manage-
ment of patients with subfertility and infertility to obtain the best possible, most
cost-effective results.
Bruno Lunenfeld, MD, PhD, FRCOG, FACOG (Hon)
Professor Emeritus, Faculty of Life Sciences, Bar-Ilan University, Israel
General Secretary, Asian Pacifi c Initiative on Reproductive Endocrinology
Pref ace

Most infertile couples will eventually attempt procedures to stimulate ovulation,
whether as fi rst-line therapy or for assisted conception. Although the process of
controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) purposes
generally requires the skilled experience of a specialist, a mono- or pauci-follicular
stimulation can and should be guided by a patient’s own gynecologist with whom
she has a longer trusting relationship. To be sure, every stimulation cycle contains
some risk for ovarian hyperstimulation and/or a multiple pregnancy, and these pos-
sibilities do create a degree of apprehension among clinicians who may be consider-
ing the procedure. In addition, as happens with most therapies that promise a
signifi cant benefi t, ovulation protocols can be fraught with so many unwieldy varia-
tions and details that many clinicians simply decline to become involved. Stimulation
of ovulation is in fact a simple treatment and quite uncomplicated for most patients.
Although there is not yet a particular accreditation or certifi cation for clinicians who
aspire to conduct classic ovulation stimulations, or even one governing the use of
COH protocols, it is nevertheless possible to assure a low-risk sequence of events to
one’s patients.
So then, how does one learn to stimulate ovulation effectively? Usually it has
been self-taught owing to inaccessibility of an experienced mentor. But the process
includes numerous decisions and choices regarding patient evaluation, gonadotro-
pin preparations, posology, protocols, duration of treatments, and when and how to
trigger ovulation. Proper, safe stimulation requires an insightful anticipation of
ovarian reactions. A clinician lacking experience to distinguish the unexpected from
the unpredictable can easily lose confi dence and focus when confronted by an
unforeseen ovarian response. As one’s practice moves to fi rmer ground, and fears of
unknown areas dissipate, it becomes easier to learn and progress from each cycle
failure without continually questioning whether a different strategy might have
yielded a better outcome.
Evidence-based consensus is generally lacking with regard to ovulation stimula-
tion, and, to some extent, there seem to be as many ways to manage certain situa-
tions as there are practitioners in the fi eld, even among those within the same clinic
team. Nevertheless, many basic rules do in fact exist, even as some might be inter-
preted by each clinician in accordance with personal views.
Thus it becomes all the more important to listen to the voices of experience. This
handbook draws upon more than 30,000 classic and IVF stimulation cycles
ix