Infertility in Practice 2022

I am pleased to present the fifth edition of Infertility in Practice, which has been updated every 5 years or
so since it was first published in 1997. Throughout this time, our understanding of infertility and its management has continued to expand rapidly. Infertility in Practice has been written as a practical guide and
is based on my experience over the last 40 years of daily clinical practice. The aim of the book is to place
the modern approach to the management of infertility in the context of sound theory and evidence-based
therapy. I have striven to provide the reader with a comprehensive classification of the causes of infertility, their investigation and their management. In this edition, I have thoroughly revised and updated the
text and completely rewritten most of the chapters.
In vitro fertilisation (IVF) has been available for almost 45 years, and, in many European countries,
2–5% of babies are the result of IVF therapy. Indeed, approximately 10 million babies have been born
worldwide from IVF, half in the last 10 years. A great deal of public attention has naturally been focused
on the high-tech advances in assisted conception therapies, yet a fundamental issue is the preconception
health of both partners, which is key both to conception, whether natural or assisted, and to the birth of a
healthy baby. I introduced preconception health in the very first edition of this book at a time when few
were addressing this important topic, and it remains just as relevant now – if not more so. In this edition,
I bring in the latest thoughts on nutritional health, periconception care and the exciting new world of the
microbiome.
Since the fourth edition of Infertility in Practice was published, there have been many advances in
the understanding and management of infertility and other updates to practice that are discussed in
this new edition – for example, a greater understanding of the pathophysiology of ovarian ageing and
ovarian reserve testing, classification of disorders of ovulation and the management of polycystic ovary
syndrome, refinement of regimens for superovulation, improved embryo culture systems and the use of
artificial intelligence for the selection of embryos, assessments for endometrial receptivity and management of recurrent implantation failure, and pre-implantation genetic testing (PGT) as a therapeutic tool,
opening up the possibility for aneuploidy screening. The clinical approach to investigation and therapy
also has made great strides to minimise the time taken to reach a diagnosis and direct a couple swiftly
to the appropriate treatment.
The field has also seen the publication of a number of evidence-based guidelines for the investigation
and management of infertility, produced variously by the British Fertility Society, the Royal College
of Obstetricians and Gynaecologists, the UK National Institute for Health and Care Excellence, the
European Society for Human Reproduction and Embryology, the American Society for Reproductive
Medicine and The World Health Organisation. It is reassuring to see a consolidation of knowledge in
an attempt to ensure evidence-based practice which, in the United Kingdom, has been used to state the
case for adequate funding of fertility care, although sadly with little effect on the decision makers in
government.
When one is determining appropriate treatment for the management of infertility, there may be one
clear treatment or several potential options. Furthermore, there are often a variety of drugs to choose
between and several potential treatment protocols. It is important to consider not only the efficacy of
treatment but also its cost-effectiveness on the basis of a combination of scientific evidence and health
economics. There has been a trend for cost-effectiveness analyses to be sponsored by the pharmaceutical
industry. Although much research could not take place without industry support, it is important to be
cautious when interpreting such data.
The treatments for most causes of infertility provide very satisfactory cumulative chances of conception and of the birth of a healthy child. However, the side effects must be borne in mind, whether it is the
immediate risk of ovarian hyperstimulation syndrome and multiple pregnancy or the long-term health
risks, such as the possibility of ovarian cancer (reassuringly not the threat it was once thought to be). In
this edition, I also discuss the outcome for children born as a result of assisted reproduction technology.
Improvements in cryopreservation technologies now enable the successful freezing of oocytes, ovarian tissue and even testicular tissue and the prospect of preserving fertility before sterilisation therapy for
cancer and other conditions. More controversial is the potential to freeze oocytes as an insurance policy
for young women who wish to delay childbearing for social reasons. This also brings with it the need
to consider an improvement in fertility education for young people at schools and colleges. In the UK,
the average age of first-time mothers is rising, and an increasing proportion of women have never had
a child (20%, compared with 10% just one generation ago). This is for a variety of reasons. And, while
approximately 15% of the population experiences fertility problems, treatments do not always work, and
their success declines with the increasing age of the woman. When people attend fertility clinics, they
are often surprised by these facts and wish they had been better informed when they were younger. The
need for fertility education arises from changing patterns of family formation in recent times, including starting families at an older age and the changing dynamics of “modern families”. Young people
feel unprepared for how best to plan their career and family, and whilst they feel they have control over
contraception, they have little idea of the various factors that may influence their fertility later in life –
whether related to lifestyle, diet, smoking and recreational drugs or the natural biological changes associated with getting older. Studies have found that adolescents do not know much about this, would like to
know more and need the information to be conveyed in a way that is engaging and helps them to integrate
it at their current life stage. For this reason, I founded the Fertility Education Initiative [1], when I was
chair of the British Fertility Society, with the aim of ensuring that people have a greater understanding
and awareness about fertility and reproductive health, so that they can make an informed choice about
their own fertility journey or that of others upon whom they may have an impact. Educational material
for teachers and animations to introduce these important topics to young people have been created [2, 3].
The whole dynamic of modern families has also changed with a greater acceptance of new ways to
create families and achieve fertility. The treatment of lesbian couples was provided by very few clinics
when I wrote the first edition of this book – an exception being my own; indeed, I have campaigned for
and achieved equal funding for same-sex couples in our region. Surrogacy for gay men is much more
common these days, as is the use of donor sperm to help single women to conceive. People with gender
identity dysphoria are also being assisted to preserve their fertility for potential use in the future.
Throughout Infertility in Practice, I comment on emerging technologies, some of which are already
being incorporated into daily practice, such as the use of pronuclear transfer for the treatment of inherited mitochondrial disorders, and other developments, such as genome editing, which brings with it
significant concerns regarding the potential abuse of such technology.
The topic of “add-ons” is vexed with emotion and concern – not least because of the lack of consensus
on what constitutes the definition of an add-on! The term has been applied to a range of procedures,
including intracytoplasmic sperm injection (ICSI), time lapse imaging, assisted hatching of embryos, the
endoscratch, acupuncture and reflexology. Some may be rooted in science but have not yet been proven
by sufficiently sized randomised trials or meta-analyses, whilst others have been proven to be ineffective
or even dangerous. People with infertility will go to any length to have a much-wanted baby, and they
can be easily enticed by misleading advertising for unproven products. Furthermore, when treatments
are often self-funded by the patients themselves, it is essential that they are not exploited by misleading
advertising.
This fifth edition of Infertility in Practice has been written during the global Covid-19 pandemic,
caused by the SARS-CoV-2 coronavirus (discussed in Chapter 1). This is still evolving and there are
many unknowns about the long-term effects of the virus, not only on population dynamics but also on
fertility and pregnancy. We have all experienced the effects of the pandemic on our health services and
also on our ability to provide fertility treatments when clinical resources, and personnel, have been so
stretched. A global vaccination programme is the way forward, and I can only hope that we will be
through these dark times by the time the sixth edition is being published.
I would like to acknowledge my partner, Grace Dugdale, from whom I have learnt so much about
preconception health, about the way in which fertility problems are often a “red flag” for other health
conditions and that reproductive health shouldn’t be seen in isolation but as part of the whole life course
for women and men. We have recently encapsulated this knowledge in The Fertility Book for patients [4].
And lastly, I wish to pay tribute to the tremendous contribution to our field of my mentor and great friend
Howard Jacobs, co-author of the first two editions of this book. I hope that wherever you work and whatever your expertise, Infertility in Practice will help in the management of couples attending your clinic.