Postmenopausal Diseases and Disorders

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Faustino R. Pérez-López
Editor

Postmenopausal Diseases
and Disorders
Editor
Faustino R. Pérez-López
Department of Obstetrics and Gynecology
University of Zaragoza Facultad de Medicina
Zaragoza
Spain

ISBN 978-3-030-13935-3    ISBN 978-3-030-13936-0 (eBook)

https://doi.org/10.1007/978-3-030-13936-0

© Springer Nature Switzerland AG 2019

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Preface

The second half of female life corresponds to the last years of the reproductive
phase and postmenopause. During this period, the specific phenomenon of the
menopause occurs, as a consequence of ovarian function cessation, converging in
parallel with physical aging. Elder women have specific risk features and disease
managements that differ from those of elder men. Therefore, it is clear that due to
these differences, medical care should be gender-based. Furthermore, gender biases
in medical research have been frequent, and many drugs have not been tested in
women before coming into the market. Therefore, it is not surprising that adverse
drug reactions are more likely to occur in women than in men due to the lack of
gender-oriented research.
Science and medicine are continuous processes characterized by the substitution
of “old” for “new” evidence. The so-called evidence-based medicine (EBM) refers
to clinical decision-making or the indication of interventions based on validated
tests or scientific data. Nonetheless, EBM cannot provide answers to all scientific
questions or, in many cases, may not provide a sufficient level of quality. Hence,
well-designed observational studies may also provide provisional recommenda-
tions—and limitations—for clinical interventions until randomized controlled trials
offer a higher level of evidence. Thus, management strategies that are based on
clinical trials undertaken in younger people or in men may not be appropriate for
postmenopausal women.
For much time, physicians and other healthcare providers have accepted as rou-
tine care those procedures and treatments that seem consolidated or free of any
discussion. However, sooner or later, uncertainties or limitations are detected, even
in the most obvious aspects, and everything is subject to revision. Therefore, science
is a perpetuum mobile, and this book has tried to collect the most rigorous and cur-
rent scientific information as a starting point to delve into each topic. The aim of this
book is to provide a practical, holistic, unbiased, and non-promotional guide for
health professionals dealing with women in their post-reproductive years.
International authors and opinion leaders cover the wide spectrum of gynecological
and non-gynecological conditions affecting post-reproductive health. Evidence-­
based information, where available, is presented, and clinical recommendations are
put into perspective. The book therefore provides an integrated approach to post-­
reproductive health.

v
vi Preface

This book includes many topics that are relevant to women’s health during their
second half of life, written by opinion leaders in their corresponding area of knowl-
edge. Each reader will jump into chapters that are closer to their quotidian area of
clinical or research interest and healthcare work. In addition, the book also expects
to serve as a consulting reference for those borderline/frontier aspects or topics that
are not so close to the daily clinical practice yet need to be reassessed or updated in
a given moment.
From time to time, we need to “pause” in order to assess where we are, and
where we want to go, to reach the best clinical approach as researchers, academics,
and healthcare providers. The authors of the different chapters have performed a
great effort in order to provide a critical analysis of the state-of-the-art knowledge,
without omitting doubts or controversies. The last years have been a time of prog-
ress in diagnosis, treatments, and integration of renovated ideas, which have not
been exempt from controversy. This book includes the best evidence possible related
to different hot topics in older women’s health. Many chapters also put into perspec-
tive clinical recommendations, always based on recent meta-analyses.
The editor wants to thank the authors for their dedication and efforts in writing
on schedule. I would also like to thank Springer Nature for their excellent and rapid
editorial assistance. The editor and the authors look forward to an international
readership taking advantage of this book to update their knowledge and improve
their clinical practice.

Zaragoza, Spain Faustino R. Pérez-López

Contents

1 Assisted Reproductive Technology in

Perimenopausal Women����������������������������������������������������������������������������   1
Nicolás Mendoza Ladrón de Guevara
and Miguel Angel Motos Guirao
2 Turner Syndrome: Primary Amenorrhea from
Adolescence to Aging �������������������������������������������������������������������������������� 19
Camil Castelo-Branco and Iuliia Naumova
3 Premature Ovarian Insufficiency ������������������������������������������������������������ 33
Agnieszka Podfigurna, Monika Grymowicz, Anna Szeliga,
Ewa Rudnicka, Marzena Maciejewska-Jeske, Roman Smolarczyk,
and Blazej Meczekalski
4 Human Papillomavirus Infection and Cancer Risk
in Peri- and Postmenopausal Women������������������������������������������������������ 53
Pedro Vieira-Baptista, Mario Preti, and Jacob Bornstein
5 Sporadic Ovarian and Fallopian Tube Cancer
in Postmenopausal Women������������������������������������������������������������������������ 79
Faustino R. Pérez-López
6 Vulvar Dermatoses and Menopause �������������������������������������������������������� 101
Joana Lyra and Pedro Vieira-Baptista
7 Bladder Pain Syndrome/Interstitial Cystitis ������������������������������������������ 121
Rui Almeida Pinto
8 Overactive Bladder������������������������������������������������������������������������������������ 133
Visha K. Tailor and G. Alessandro Digesu
9 Management of Female Stress Urinary Incontinence���������������������������� 145
Giampiero Capobianco, Pier Luigi Cherchi, and Salvatore Dessole
10 Screening and Management of Female Sexual Dysfunction
During the Second Half of Life ���������������������������������������������������������������� 165
Ana M. Fernández-Alonso, Marcos J. Cuerva, Peter Chedraui,
and Faustino R. Pérez-López

vii
viii Contents

11 Current Treatment Modalities for the Genitourinary

Syndrome of Menopause �������������������������������������������������������������������������� 187
Cemal Tamer Erel
12 Laser Treatment for Vulvovaginal Atrophy�������������������������������������������� 205
Marco Gambacciani
13 Laser Treatments in Female Urinary Incontinence�������������������������������� 211
Ivan Fistonić and Nikola Fistonić
14 Metabolic Syndrome and Excessive Body Weight
in Peri- and Postmenopausal Women������������������������������������������������������ 225
Andrea Giannini, Maria Magdalena Montt-Guevara,
Jorge Eduardo Shortrede, Giulia Palla, Peter Chedraui,
Andrea Riccardo Genazzani, and Tommaso Simoncini
15 Metabolic Syndrome and Atherosclerosis in Nondiabetic
Postmenopausal Women���������������������������������������������������������������������������� 237
Stavroula A. Paschou, Panagiotis Anagnostis, Dimitrios G. Goulis,
and Irene Lambrinoudaki
16 Polycystic Ovary Syndrome-Related Risks
in Postmenopausal Women������������������������������������������������������������������������ 249
Panagiotis Anagnostis, Stavroula A. Paschou, Irene Lambrinoudaki,
and Dimitrios G. Goulis
17 Sleep and Sleep Disturbances in Climacteric Women���������������������������� 261
Päivi Polo-Kantola, Tarja Saaresranta, and Laura Lampio
18 Impact of Menopause on Brain Functions���������������������������������������������� 283
Alice Antonelli, Andrea Giannini, Marta Caretto,
Tommaso Simoncini, and Andrea R. Genazzani
19 Vasomotor Symptoms: Clinical Management���������������������������������������� 295
Maria Celeste Osorio-Wender and Mona Lúcia Dall’Agno
20 Vasomotor Symptoms, Metabolic Syndrome,
and Cardiovascular Risks ������������������������������������������������������������������������ 305
Pauliina Tuomikoski and Hanna Savolainen-Peltonen
21 Menopause and Age-Related General Health Risk:
A Woman’s Heart Needs Her Hormones ������������������������������������������������ 315
Adam Czyzyk and John C. Stevenson
22 Menopausal Hormone Therapy to Prevent Chronic Conditions���������� 327
Rafael Sánchez-Borrego
23 Selective Estrogen Receptor Modulators (SERMs):
State of the Art ������������������������������������������������������������������������������������������ 349
Santiago Palacios
Contents ix

24 Management of Osteoporosis in Postmenopausal Women�������������������� 367

J. J. Hidalgo-Mora, Antonio J. Cano-Marquina,
A. Szeliga, Miguel Ángel García-Pérez, and A. Cano
25 Anabolic Agents for the Treatment of Postmenopausal
Osteoporosis������������������������������������������������������������������������������������������������ 387
Salvatore Minisola
26 The Links Between Osteoporosis and Sarcopenia in Women���������������� 395
Juan Enrique Blümel, Eugenio Arteaga, María Soledad Vallejo,
and Rosa Chea
27 Female Sarcopenic Obesity ���������������������������������������������������������������������� 405
Fidel Hita-Contreras
28 Cognitive Decline in Women: The ZARADEMP Study ������������������������ 423
Patricia Gracia-García, Elena Lobo, Javier Santabárbara,
Concepción de la Cámara, and Raúl López-Antón
29 Managing Menopause and Post-­reproductive Health:
Beyond Hormones and Medicines������������������������������������������������������������ 439
Skye Marshall and Margaret Rees
30 Effects of Exercise on Menopausal Prevalent Conditions���������������������� 467
Samuel J. Martínez-Domínguez, Juan Bueno-Notivol,
Peter Chedraui, Vanesa Alonso-Ventura, Julia Calvo-­Latorre,
and Faustino R. Pérez-López
Assisted Reproductive Technology
in Perimenopausal Women 1
Nicolás Mendoza Ladrón de Guevara
and Miguel Angel Motos Guirao

1.1 Fertility and Aging

1.1.1 Age as a Social Factor of Infertility

If we analyze the demographic progression that took place in Europe in the last
century, we observe a clear secular trend toward a decrease in the birth rate and an
increase in maternal age. As an explanation of this, it seems that a purely cultural
reason stands out: the postponement in the desire for genesis, which, in many cases,
occurs for a variety of employment, social, and economic reasons. On the other
hand, advances in assisted reproduction allow pregnancy at any age, and we face
new ethical and health challenges regarding the question of what is the limit for a
woman to become pregnant. It is shown that age decreases fertility due to factors
such as [1, 2]:

• A decrease in the number of oocytes

• A decrease in the frequency of intercourse
• A decrease in oocyte quality
• A decreases in sperm quality

1.1.2 Problems in Fertility and Pregnancy Derived from Age

Fertility declines with the passage of time, particularly after 35 years. A decline is
seen in both the number and quality of the reserve of ovules, which increases the
difficulty for pregnancy and the risk of spontaneous abortions (more than 50%) and
of fetuses with chromosomal abnormalities (e.g., Down’s syndrome) [3].

N. Mendoza Ladrón de Guevara (*) · M. A. Motos Guirao

Department of Obstetrics and Gynecology, University of Granada, Granada, Spain
e-mail: [email protected]; [email protected]

© Springer Nature Switzerland AG 2019 1

F. R. Pérez-López (ed.), Postmenopausal Diseases and Disorders,
https://doi.org/10.1007/978-3-030-13936-0_1
2 N. Mendoza Ladrón de Guevara and M. A. Motos Guirao

As age itself is the factor that most influences the rate of spontaneous pregnancy
and the outcomes of fertility treatments, in people over 35 years of age, it is not
recommended to wait a year to see a specialist; instead it is advisable to take matters
into their hands after 6 months of trying to conceive. In people aged over 40 years,
it is recommended to seek help immediately [4].
The application of assisted reproductive techniques (ARTs) is very common
in this age group, with a strong tendency to resort to egg donation. This
also prevents the increased risk of fetuses with chromosomal abnormalities
(the age of the oocyte is that of the donor), but not that of other pregnancy
complications such as gestational diabetes, hypertension, intrauterine growth
restriction, placental pathology, and prematurity, which continue to depend
on the mother’s age. Multiple pregnancies are also more frequent, because of
the greater number of embryos transferred. As a consequence, the numbers
of operative or instrumental deliveries and perinatal and maternal morbidity/
mortality are all increased during perimenopause [5].

1.1.3  p to What Age Is Pregnancy Allowed with Fertility

U
Treatments?

Progress in reproductive medicine and in obstetrics itself has raised another

important debate regarding age: what is the age limit to conceive or to apply an
ART? Certain healthy habits and the feeling of staying young and being prepared
for all eventualities have triggered the demand for fertility treatments for women
over 40. Oocyte donation makes this a possibility even for those who have crossed
the border into menopause. Since uterine age does not correspond to ovarian age,
the maternity departments are now full of “older” women, an example of how
advances in medicine appear to have developed ahead of the necessary and slow
process of legislation and ethics. An older woman, even being postmenopausal,
may not feel too old to have a child and may offer the infant a better education
now that she no longer has the financial or emotional needs of younger women
[6].
However, one of the immediate consequences of an increase in pregnancies
in older women is the greater demand for medical and psychological assistance,
since there are fewer requests for prenatal diagnostic methods, practices to reduce
stress, and voluntary interruptions of pregnancy, along with an increase in perinatal
and maternal morbidity and mortality, not to mention the concern for raising
grandchildren instead of children.
There is an open debate on whether or not a child’s upbringing is optimal at
these ages. In particular, some people are shocked to see older women breastfeeding
their babies in the nonscientific press, while others warn of the high risk of leaving
them as orphans at a young age. In the future vision of our own wellbeing, there are
even those who argue that it is preferable to have children—regardless of the age
at which they are conceived—to increase the birth rate. In their arguments in favor
it is pointed out that they will take care of our care when we are elderly. And even
1 Assisted Reproductive Technology in Perimenopausal Women 3

when the argument seems to have tilted on the side of those who accept as logical,
and even normal, a pregnancy over 40 years, common sense should still prevail
when it comes to putting a cap on this demand. Although there is no clear limit, it
seems to be ethical and medically advisable to place this limit before the age of 55,
but it is more reasonable to place it at 50 years, given the high risk of cardiovascular
morbidity from that age [7].

1.1.4 Social Controversies of Infertility Treatments

Of all the areas of medicine and all the attributes that have conditioned the evolution
of our species, it is without doubt that sexuality and reproduction are those that are
most loaded with social singularities. In addition, the rapid advance of reproductive
technology has introduced significant changes in the conception of families that
is sometimes difficult to assimilate within less advanced societies and those most
impregnated with extreme conservatism. Some common practices in reproductive
medicine have also generated controversies, such as the donation or freezing of
gametes and embryos, embryonic reduction, or the costs of these treatments for the
health system.

1.1.5  he Sociocultural Acceptance of the New Models

T
of Families that Emerged with ARTs

From the first birth achieved with ART, what appears to have been most scandalous
certain groups is the change in the classic conception of family, that is, two-parent,
heterosexual, within a religious or civil commitment, and with the transmission of
one’s genes to the offspring.
We can see then how far the concept of family to which we have become
accustomed has shifted in the new millennium. It is now seen as nothing more
than cohabitation with single-parent families, those of homosexual couples with no
legal ties or where genes other than those of legal parents are transmitted. In this
regard, in countries where surrogacy is allowed, it can be possible for a baby to
theoretically have five parents: the donor of the ovule, the sperm donor, the woman
who has gestated the child in surrogacy, and the legal parents who have requested
the treatment. Improvements in laboratory techniques for the cryopreservation of
gametes or embryos have even made it possible for one parent to be deceased. There
is no doubt that popular fantasies have been triggered and that continued discussion
of these issues will cause perplexity.
Now that ARTs are common throughout the world, the medical, legal, moral,
and ethical debates unleashed since their inception have been globalized. Some
countries, like Spain, have regulated these by taking into account the clinical
recommendations, but in other latitudes and within the groups of immigrants with
whom we live, there are opinions of a religious nature that prevail in the deemed
suitability and use of these methods [8].
4 N. Mendoza Ladrón de Guevara and M. A. Motos Guirao

1.2 Infertility Generalities

Infertility is a generic term that refers to the problems that reduce human fertility
and that, in the strictest sense, is considered a disease. From an epidemiological
perspective, infertility is considered a frequent phenomenon. It is estimated that
(i) infertility affects some 70–80 million couples around the world, that 15% of
those living in Western countries will consult for it, and (ii) that in these more
advanced societies, there is a growing group of men and women who already have
at least one child but wish to have another. There is a direct relationship between
certain social and lifestyle factors and fertility and infertility: age; use of tobacco,
alcohol, caffeine, marijuana, cocaine, and other drugs; use of anabolics; obesity;
and psychological stress.

1.2.1 Diagnosis of Infertility

1.2.1.1 When to Diagnose Infertility?

In the absence of previous indications, couples who have been trying to become
pregnant for more than 1 year should begin testing and therapeutic measures.
An exam should be conducted when the woman is over 35 years old or if there
is a history of menstrual rhythm disturbances or suspicion of uterine, tubal, or
endometriosis pathology, as well as when the male has a history of cryptorchidism
or other testicular pathology.

1.2.1.2 What Is the Basic Infertility Test?

This test consists of establishing a complete clinical history, a menstrual history,
a general exam, preconceptional advice, and coital counseling. The exam must
be given to both members of the couple. During the infertility test, cost-effective
measures should be considered, being as minimally invasive as possible and
conducted in accordance with the wishes of the two partners. The causes of
infertility are varied and, in many cases, are multiple. This almost always involves
both members of a couple. The tests included for infertility are gynecological exam
and cytology, ultrasound of the uterus and ovaries, basic seminogram, tubal X-ray
(hysterosalpingography), and hormone and ovarian reserve study. In cases where
another alteration is suspected and other fertility treatments have failed, other tests
may be performed, such as advanced hormonal study, cervical or vaginal cultures,
hysteroscopy, advanced seminogram and sperm DNA fragmentation test, and study
of coagulation disorders.

1.2.1.3 Monitored Anamnesis in Reproductive Medicine

For female patients, evaluation of anamnesis in reproductive medicine considers
parity, obstetrical outcomes, age at first menstruation, menstrual formula,
dysmenorrhea, contraceptive methods used, number of sexual relationships, length
of infertility and previous treatments, previous surgeries and illnesses, gynecological
history, allergies to medication, lifestyle habits (such as use of tobacco, alcohol,
1 Assisted Reproductive Technology in Perimenopausal Women 5

drugs, diet, and frequency of exercise), occupation (and any associated stress), and
family history. For male patients, anamnesis includes information about children
from a previous partner (having other children does not exclude the potential for
infertility), length of infertility and results from previous studies and treatments,
previous surgeries and illnesses, medication allergies, lifestyle habits (such as use
of tobacco, alcohol, drugs), occupation (and any associated stress), and family
history.

1.2.1.4 D iagnosis of Ovarian Function and the Hypothalamic-­

Gonadal Axis
Evaluate ovarian function, menstrual history, basal temperature, cervical mucus,
serum progesterone, urinary luteinizing hormone (LH), follicular development,
endometrial thickness and appearance, and analysis of androgens, thyroid hormones,
prolactin, and gonadotropins. Conduct a transvaginal ultrasound.

1.2.1.5 Study of Ovarian Function

The evaluation of ovulatory function is an important part of the basic infertility test.
However, we do not have any evidence that accurately assures us that ovulation
has occurred except, obviously, pregnancy. This says a lot about the variability and
false-positives of many of the tests that are routinely used in the clinic. A history of
regular cycles corresponds to correct ovulation in 97% of cases.

1.2.1.6 The Test of the Ovarian Reserve

Although age is the main prognostic factor of female fertility, in recent decades,
motherhood has been possible for older women, which has changed our usual
practice in the fertility clinic such that the analysis of the ovarian reserve
has become one of the basic pillars upon which an adequate diagnosis and
reproductive prognosis can be reached. Parameters for evaluating the ovarian
reserve include biochemical markers such as follicle-stimulating hormone (FSH),
estradiol (E2), inhibins A and B, and, more recently, the anti-Müllerian hormone
(AMH). Ultrasound markers include the ovarian volume, the number of antral
follicles, and the flow of the uterine artery. In addition, some dynamic tests have
been designed to improve the prognosis of those using drugs commonly used
in ovarian stimulation (clomiphene, exogenous FSH, or gonadotropin-releasing
hormone (GnRH) analogues). These tests measure the variation of endogenous
FSH, estradiol, and inhibin. Although they have been able to improve the
sensitivity of the test, the increase is not sufficient to justify the expense and
exposure to the established drug. AMH derives its name from its capacity to
cause the regression of the conduits of Müller during masculine differentiation. In
women, the AMH has a great paracrine power. The function of AMH is to inhibit
the growth of nondominant follicles, with its local concentration increasing until
reaching maximum levels in the antral follicles. Consequently, the measurement
of AMH is a reflection of follicular activity, and as its peripheral blood values
do not fluctuate as much as other hormones, it is used as an excellent ovarian
reserve marker.
6 N. Mendoza Ladrón de Guevara and M. A. Motos Guirao

1.2.1.7 Indicators of Ovarian Reserve

Biochemical indicators of ovarian reserve include FSH, estradiol, inhibins A and B,
testosterone, and AMH. Indicators observable by ultrasound include the number of
antral follicles and the volume of the ovary. Dynamic tests may include clomiphene
testing, exogenous FSH ovarian reserve testing, response of inhibin and E2 to
exogen FSH, and testing the response of inhibin and E2 GnRH analogues. These
various tests comprise the different ovarian reserve indicators. In summary, the most
accurate are the ultrasound counts of antral follicles and the measurement of AMH;
the least expensive are the ultrasound counts of antral follicles and the basal value
of FSH and E2 (between the first and third day of the cycle); dynamic tests do not
provide benefits compared with biochemical indicators or ultrasound tests and are
expensive while remaining unable to predict the age of menopause presentation.
Dynamic tests are only useful for offering a reproductive prognosis in women who
plan to undergo fertility treatment.

1.2.2 Causes of Infertility

1.2.2.1 Ovarian Factors

The evaluation of ovulatory function is important as a first measure in basic infertility
testing because it corresponds to 15–25% of the causes of infertility. A history of
regular cycles corresponds to ovulation in 97% of the cases. A confirmed pregnancy
is the only way to establish that ovulation actually occurred due to the great variability
and false-positives involved with other tests. When an ovulatory dysfunction is
diagnosed and a pharmacological treatment is indicated after 3–6 months without
getting pregnant, another possible cause of infertility must be investigated. As a
general rule, when the woman has regular cycles, ovulation is likely to be correct.
When irregular cycles are presented, we can measure progesterone in the second
phase or request a graph of basal temperature.
A prolactin measurement routine is not necessary unless there are menstrual
abnormalities, galactorrhea, or suspected pituitary tumor. Similarly, patients with
anovulation have a higher proportion of presenting with thyroid disease, but thyroid-­
stimulating hormone will only be measured when this disease is suspected. The
assessment of the ovarian reserve is made in certain cases of patients over 35 years
of age or with the intention of providing them with a prognosis or additional
information to decide on possible treatments. An FSH lower than 10 mIU/mL with
E2 less than 30 pg/mL reflects a normal follicular reserve status.

1.2.2.2 Uterine Factors

The cervical factor is a rare cause of infertility. The postcoital test is the classic test
that determines it, but there is great interobserver variability, and it is not necessary
to routinely carry this out because it has no prognostic value and is not indicative
of any type of therapy. Although uterine malformations are not usually a cause of
infertility, examining the uterine cavity should be part of a basic infertility test. This
1 Assisted Reproductive Technology in Perimenopausal Women 7

should be done in an individualized manner, according to other previous findings,

and should be based on a transvaginal ultrasound. In case of suspicion of organic
pathology (polyps, submucosal fibroids, hyperplasia), a hysterosonography or a
hysteroscopy will be requested.

1.2.2.3 Tubal and Peritoneal Factor

Tubal obstruction is responsible for infertility, either as a single cause or accompanied
by other causes in 30% of cases. The tubal factor should be investigated when other
infertility factors have been ruled out because the test that determines it, called the
hysterosalpingography (HSG), is an invasive and often painful technique. Of course,
if in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is planned,
HSG is not needed. For the study of tubal factor, the HSG is the least invasive
and most cost-effective form, allowing diagnosis of tubal obstructions (proximal
or distal) and evaluation of the uterine cavity. It is done in the first phase of the
cycle before ovulation. If screening for chlamydial infection has not been done,
antibiotic prophylaxis must be carried out. However, it is not precise in detecting
peritubal adhesions and for diagnosing a peritoneal endometriosis, in which case it
is indicated to perform a laparoscopy if there are strong suspicions of endometriosis,
tuboperitoneal adhesions, or important tubal pathology.

1.2.2.4 Male Factor

The minimum evaluation of the male should include a complete medical history, a
physical exam, and at least two seminograms separated 3 months from each other that
should be initiated before subjecting the woman to any type of invasive exam, such as
HSG. The seminogram is the main test in the study of the male factor, and abstinence
is recommended for 2–3 days. The seminogram offers basic information on seminal
volume, concentration, mobility, and sperm morphology. Unless the laboratory has
its own criteria, it is recommended to follow the 2010 WHO guidelines.

1.2.3 Techniques for Assisting Reproduction

1.2.3.1 What Is Artificial Insemination (AI)?

Broadly speaking, AI involves the introduction of semen into the uterus, which
is why it is also called intrauterine insemination. We distinguish the conjugal AI
(CAI), meaning it is from the male partner, from donor AI (DAI). We have used the
word “capacitated,” which is an important part of these ART. Indeed, for a sperm to
acquire the ability to cross the membrane that surrounds the ovum and fertilize it, it
must first undergo biochemical modifications in the most distal part of its head in a
region called the acrosome. This phenomenon occurs naturally when the acrosome
passes through the cervix and is imitated in the laboratory before being deposited
inside the uterine cavity. Sometimes we use it as a diagnostic method known as a
training test, and it helps us assess whether a patient’s semen is valid for proposing
a conjugal AI.
8 N. Mendoza Ladrón de Guevara and M. A. Motos Guirao

1.2.3.2 What Are the Indications of AI?

It can be supposed that all semen qualifies for CAI. In each clinic or unit of human
reproduction, there are criteria to decide if the seminogram, as the analysis is called,
is normal or has some alteration and also if it is valid or not for a CAI or even
IVF or ICSI. Some centers have their own criteria for defining seminograms, and
although few do, they must be centers where there is a researcher who has previously
published such criteria in specialized journals. For this reason, the majority of
reproduction laboratories use the WHO’s criteria, which are periodically renewed.
The latest revision is available online.

1.2.3.3 What Is IVF and ICSI?

When IVF or an ICSI is proposed, the two gametes (oocytes and sperm) are needed
in the reproduction laboratory to perform the fertilization, which is why it is called
in vitro. According to the latest data collected by the Spanish Society of Fertility, the
pregnancy rate per transfer is close to 40%. These techniques require the training
and accreditation of the personnel in charge (gynecologists and embryologists) and
are planned in a series of steps:

1. Follicular development: recruitment (rescue) and growth of one or more follicles,

the structures of the ovary where the oocytes mature. Development is usually
stimulated by a medication that contains gonadotropins, the natural female
hormones responsible for follicular development. The process may be controlled
with ultrasound and hormonal analysis.
2. Obtaining the oocytes. The vagina is punctured, and the process of obtaining
the oocytes is guided by ultrasound. The follicles are punctured, and their
liquid content (follicular fluid) is suctioned where the oocytes supernate.
Although it can be performed under local anesthesia, sedation of the patient is
preferred in many centers so that the patient does not suffer pain from the
puncture.
3. In vitro fertilization (IVF). Fertilization itself occurs when the microinjection
(ICSI) or its modern variant is performed with the extension of the microscopic
vision and the selection of the sperm with better morphology (intracytoplasmic
morphologically selected sperm injection).
4. Embryo transfer. Once the oocytes are fertilized, the resulting embryo or embryos
are transferred into the uterus in a maneuver similar to that of AI. They are usu-
ally scheduled 2–6 days after the follicular puncture, and those that are not cho-
sen for the transfer are cryopreserved for another attempt. The criteria to decide
which are transferred and which are frozen are morphological, and each repro-
duction center usually has its own scale to catalog its quality. The number of
embryos to be transferred is controversial and generates uncertainty in patients.
The transfer of more than three embryos is not allowed and for ethical reasons it
is often recommended to limit this to only one, although this restricts the per-
centage of pregnancies.
1 Assisted Reproductive Technology in Perimenopausal Women 9

1.2.3.4 What Is Preimplantation Genetic Diagnosis?

Preimplantation genetic diagnosis (PGD) was developed as a technique to find
out the sex of embryos with a test that detects the Y chromosome in the selected
embryonic cells. Evidently, the determination of sex is not the purpose of this
technique, but rather its purpose is the location of genetic defects transmitted by
the X chromosome. Since the 1990s then, its use has expanded to other genetic
diseases. Undoubtedly, the PGD has proved to be an extraordinary step, both for the
knowledge of embryonic development and for the infertility and infertility clinic.

1.3 Genetics in Assisted Reproduction

1.3.1 Genetic Counseling and Consultation of Clinical Genetics

Genetic counseling “is a communication process that deals with the human problems
associated with the occurrence, or the risk of occurrence, of a genetic disorder in
a family” [9]. It is based on medical, reproductive, and family history and must
always be carried out. In assisted reproduction, risk assessment includes not only
the embryo and the fetus but also the parent itself. In this way, it is necessary to
assess the possibilities of giving birth to a child with congenital malformations or
genetic diseases and even their long-term appearance (e.g., genomic imprinting
diseases), but for this it is necessary to study thoroughly the causes of infertility of
the couple and their genetic, personal, and family clinical history. The information
must be obtained in a systematic way, and, although the autonomy of the couple
prevails, in cases of doubt, the interests of the future children must be put before
them. Genetic counseling is always nondirective and is an essentially medical act,
although other health professionals may be involved. Today it is not possible to
carry out any genetic study detached from genetic counseling, and, in turn, genetic
counseling should not be carried out outside the context of medical consultation.
This consultation must be conducted by a clinical geneticist and has a multiple
purpose—diagnostic, prognostic, preventive, and therapeutic—since it helps
­
to choose the ideal reproduction technique in each case. The consultation also
serves the purpose of performing comprehensive genetic counseling and obtaining
informed consent for any genetic measure that is to be adopted. In a structured way,
the pretest objectives are as follows:

• Obtaining the genetic medical history

• Report and evaluation of the genetic-reproductive risks of the couple
• Forecast report of future genetic tests
• Evaluation of the results of genetic and complementary tests
• Report of the reproductive genetic counsel
• Genetic eligibility report
• Obtaining the informed consent of genetic tests