Table Of ContentNFOG - Nordic Federation of Societies of Obstetrics and Gynecology
Preface
This is an electronic textbook (e-textbook) aimed for medicial students and published by Nordic Federation of Societies of Obstetrics
and Gynecology (NFOG)
Editorial guidelines
The following principles were used for compiling this e-textbook.
Text, illustrations, learning principles to be aligned with the curricula for obstetrics and gynecology in Nordic medical schools (and
and the needs of GPs and junior doctors outside our specialty).The textbook is not aimed at trainees in obstetrics and gynecology or
midwives.
Author fee: none.
Availability: On the internet, for computer, tablet and smartphone. No paper version published.
Based on modern pedagogic principles not addressed in traditional printed books.
Free access to the platform (open source).
Each chapter written by a set of subspecialist authors from three or more Nordic countries. NFOG appreciate these contributions
very much. Remember that the authors did not receive any royalty. Thank you so much.
During development of the chapters, differences in the clinical guidance in the Nordic countries was noted by the authors and the
editorial committee. Therefore, there may be some clinical perspective in this e-textbook that have been developed after consensus
between the authors of each chapter and with the editorial committee, and contents may thus differ in some aspects from national
guidelines.
Editorial committee
Ulla Breth Knudsen, MD, Professor, PhD, Denmark.
Niels Uldbjerg, MD, Professor, DMSc, Denmark.
Kristina Gemzell-Danielsson, MD, Professor, PhD, Sweden.
Jone Trovik, MD, Professor, PhD, Norway.
Oskari Heikinheimo, MD, Professor, PhD, Finland.
Thora Steingrimsdottir, MD, Professor, PhD, Iceland
Editorial secretary
Rebekka Svarrer, MD, Denmark
Illustrator
Lotte Clevin, MD, Denmark
Video Editor
Jørgen Præst, consultant emeritus, Aarhus University Hospital, Aarhus, Denmark
Language revision
Reynir GeirssonPhD, FRCOG, professor em, Iceland
NFOG-MCQ
Thomas Jensen, medical student, PhD student, Denmark.
Contact e-mail
[email protected] • The editorial board will appreciate feed-back and suggestions.
Electronic platform
• Sundhed.dk, owned by Danske Regioner, Sundheds- og Ældreministeriet, and Kommunernes Landsforening, Dampfærgevej 22, 2100
Kbh Ø, Denmark
References to external resources, example
Morin-Papunen L, Vanky E and Ravn P. <Year of publishing>. <Name of resource>. <Location and publisher>
https://www.sundhed.dk/sundhedsfaglig/opslag-og-vaerktoejer/laereboeger/obstetrics-gynecology/
ISBN: 978-87-972596-0-3
References to the NFOG-e-textbook (can be used by the authors for their CV)
Nordic Federation of Obstetrics and Gyneocology, NFOG (2020): NFOG-e-textbook.
From: https://www.sundhed.dk/sundhedsfaglig/opslag-og-vaerktoejer/laereboeger/obstetrics-gynecology/
• A chapter in the NFOG-e-textbook
Bergholt, Thomas, Malin, Dogl, Aura, Pyykönen, Kristensen, Steffen Anesto (2020, August): Induction of labor.
From: https://www.sundhed.dk/sundhedsfaglig/opslag-og-vaerktoejer/laereboeger/obstetrics-gynecology/
Opdateret 29.06.2021
Indhold leveret af:
NFOG - Nordic Federation of Societies of Obstetrics and Gynecology
Ole Mogensen Department of Obstetrics and Gynecology - Aarhus University Hospital
8200 Århus N
Telefon: +45 30 71 45 62
[email protected]
NFOG - Nordic Federation of Societies of Obstetrics and Gynecology
1. Women’s Global Health
Take home messages
There is still a long way to go to reach equal rights and acceptance of both genders and to provide girls and women in all parts of the
world with the possibility of education and control over their reproductive health and lives. Early and unintended pregnancy jeopardizes
the prospect of pursuing education and a career, and thus perpetuates cycles of poverty. There is all reason to state: Women’s rights =
human rights!
More than 200 million women lack access to modern contraception. Globally, unsafe abortions are estimated to contribute to 8-13
percent of all maternal deaths. With access to contraception, safe abortion and post-abortion care, 18 percent of maternal mortality
could be avoided with enormous individual as well as health economic consequences.
Geographical, financial and cultural barriers to free, appropriate, evidence-based and timely care are still the main reasons for maternal
and neonatal mortality and morbidity. “Women are not dying because of diseases we cannot treat. They are dying because societies have yet
to make the decision that their lives are worth saving.” (Professor M.F. Fathalla, former President of FIGO, Professor of Obstetrics and
Gynaecology, Assiut University, Egypt, 1998)
Economic and political instability, migration, conflicts and wars have reversed the improvements made in recent decades. Migrant and
refugee women are especially vulnerable and face sexual violence, abuse and trafficking. Covid-19 has seriously worsened living
conditions for girls and women in all countries.
In Sub-Saharan Africa and parts of Asia and South- and Central-America the lack of access to professional obstetrical care is associated
with complications, including a high frequency of obstetric fistulas. In contrast a global epidemic of unnecessary cesarean section
increases maternal and newborn morbidity and mortality.
Maternal and neonatal mortality
Maternal mortality is defined as the death of a woman during pregnancy or childbirth within 42 days of termination of pregnancy.
Complications from unsafe abortion significantly contribute to the global maternal mortality and morbidity. In 2017 the maternal
mortality ratio (MMR) was 211 deaths per 100 000 live births. The global number of maternal deaths was 295 000 (UN statistics). Sub-
Saharan Africa has the highest figures with 415 maternal deaths per 100 000 live births. For comparison, the MMR in the Nordic
countries was 3-5 deaths per 100 000 live births. Globally, 70 000 women die annually due to postpartum hemorrhage, the leading
direct cause of maternal death (WHO). Other causes include high blood pressure/pre-eclampsia, infections and other complications of
delivery and unsafe abortions.
The World Bank estimates that 80% of deliveries were conducted by skilled birth attendants in 2018. However, the staff´s ability to
provide appropriate care is highly dependent on resources and the settings in which they work. Access to skilled health professionals for
antenatal, birth and postnatal care, immunizations, and to clean water, sanitation, hygiene, are vital factors for reducing maternal and
child mortality.
Figure 1. Click to magnify. Antenatal care
Women of color and women from minority groups have a higher risk of dying from pregnancy related complications compared to the
majority women, even within the same countries. Afro-American women in the USA have a 3-fold risk of pregnancy related fatalities
compared to white women; racial bias being one of the reasons. This underlines the need for healthcare to be an integrated part of the
social structure in a country in order to meet the needs of all; regardless of class, ethnicity or financial means.
Sadly, health workers are also part of the problem. In many countries women are met with disrespect and physical abuse when seeking
obstetric care, especially unmarried women. Research shows that poor and underprivileged women are at high risk for harassment,
coercion and neglect by trained staff.
WHO statement on this under reported problem is available here
Maternal health care and neonatal mortality go hand in hand. Neonatal deaths during the first 28 days of life accounted for almost a half
of the under-5 deaths in 2017. Preterm birth, intrapartum-related complications, infections and birth defects cause the majority of
fatalities during the first four weeks of life. The global neonatal mortality rates (NMR) decreased by 51% from 36.6 per 1000 livebirths in
1990 to 18.0 deaths per 1000 livebirths in 2017. Neonatal mortality in the Nordic countries is <2 deaths per 1000 livebirth.
Figure 2. Woman cuddling her newborn
Figure 3. Click to magnify. Newborn in incubator in high-resource neonatal intensive care unit (NICU)
Lessons learned from the Nordic countries are that maternal and neonatal mortality declined long before medical interventions like
antibiotics and extensive use of cesarean sections. The improvements came as results of political and social reforms allowing girls to
enter higher education thus postponing first pregnancy, but most importantly; access to free health care in pregnancy, childbirth and
abortion.
Maternal morbidity due to the low/high rates of cesarean section
Obstetric fistula (for description of fistula see the chapter Urinary incontinence) is the result of prolonged or obstructed labor, when the
unborn baby cannot pass through the pelvis. It can be prevented by timely access to obstetric care including cesarean section (CS).
Obstetric fistula leaves women incontinent for urine and/or feces, and inflicts shame, social isolation and health problems like frequent
infections, kidney disease, painful sores and infertility. WHO estimates that annually between 50 000 to 100 000 women are affected by
obstetric fistula. Further; 2 million young girls live with untreated obstetric fistula in Asia and Sub-Saharan Africa with limited access to
operative treatment. The cesarean section rate in Sub-Saharan Africa is still as low as 5% of all deliveries.
In contrast, in many parts of the world there is an increasing concern due to the CS epidemic. This is highlighted in the International
Federation of Obstetrics and Gynecology (FIGO) position statement: How to stop the Cesarean Delivery Epidemic. Worldwide rates of
CS have increased from 6% in 1990 to 21% in 2015. Rates in the Northern part of Europe are still below 20%, whereas in the South
Eastern part of Europe, Egypt, China and South America more than 50% of deliveries are conducted via cesarean section. CS is associated
with direct maternal and newborn morbidity and mortality, and newborns have an increased risk from iatrogenic preterm delivery. Severe
consequences for future pregnancies include an increase in spontaneous preterm birth, uterine rupture and abnormal placentation,
which may result in excessive maternal bleeding and need for hysterectomy. WHO has concluded that at population level, cesarean
section rates higher than 10-15 % are not associated with improvement of maternal and newborn outcomes.
Figure 4. Click to magnify. Caesarean section: the newborn held up for the parents to see!
Adolescent reproductive health
In 2018 the population of people aged 10-24 years was 1.2 billion, almost 90% of whom live in low- or middle resource countries. India
and China together account for one-third of the adolescent population, however, with very different demographic profiles: From 1990 to
2016 China´s adolescent population decreased by 28% whereas in India it increased by 40%. In the years to come, the greatest increase in
adolescent population will be seen in low-resource regions like Sub-Saharan Africa and South Asia.
Adolescent pregnancy has considerable negative consequences. It leads to dropping out of school, to poverty and limits the possibility
for girls to achieve their full potential.
Figure 5. Click to magnify. A teenage mother taking care of her toddler
Figure 6. Click to magnify. While her friends attend primary school
Every year over 20 million girls aged 15 to 19 years and 2 million girls under 15 years give birth; the majority living in low-resource
countries. Of these young mothers 90% are married. Compared with mothers aged 20-24 years, girls aged 10-19 years are at higher risk
for pregnancy- and delivery-related complications, including obstetric fistula and death. However, the pattern of age-specific maternal
mortality is J-shaped for all regions apart from Southeast Asia, and it is to be noted, that globally the risk for maternal mortality is the
highest in women older than 30 years. This is a cause for concern due to the increasing age of primiparous women in many of high-
resource countries.
Female genital mutilation (FGM) comprises all procedures that involve partial or total removal of the external female genitalia, or other
iatrogenic trauma to the female genital organs for non-medical reasons (WHO). Girls are subjected to FGM in 30 countries, mainly in
Africa, as well as in the Middle East and Asia. FGM is mostly carried out on young girls between infancy and age 15. FGM is both a
physically and psychologically traumatic procedure and can inflict serious gynecological and obstetric long-term consequences.
A positive change of attitudes is seen in many countries with an overall decline in the prevalence of FGM. UNICEF has estimated that in
2016, 200 million girls and women had undergone FGM, and there are over 3 million girls at risk of undergoing the procedure every year.
FGM is illegal in many countries including the Nordic countries. However, only Iceland has legislation that also protects male children
against non-therapeutic procedures causing permanent bodily alterations (see also Female genital mutilation in the Sexual violence
chapter).
Cervical cancer is the fourth most common cancer in women, ranked after breast, colorectal and lung cancers. WHO has launched a
st
Global Initiative to eliminate cervical cancer as a public health problem during the 21 century. Persistent human papillomavirus (HPV)
infection is the main cause of cervical cancer and therefore, the most effective intervention is prophylactic HPV vaccination. The ambition
of WHO is to vaccinate 90% of girls by age 15 years. In many countries HPV vaccination is part of the national vaccination program, and it
is increasingly offered to both girls and boys usually at ages 11-12, including in the Nordic countries (see also the chapters on
Premalignant lesions of the uterine cervix and on Gynecological cancer).
Contraception and abortion
It has been estimated that over 200 million women, - one-third of them aged 15-24 years, do not have access to acceptable and
effective contraception.
Figure 7. Click to magnify. Contraception devises
Annually almost 4 million girls aged 15 to 19 years undergo unsafe abortion. Roughly half of all unintended pregnancies end in abortion,
the majority in countries with strict abortion legislation which also includes limited access to contraception and sexuality education. The
indirect costs of unsafe abortion include the loss of productivity, secondary infertility, social stigma and other socio-psychological
consequences.
Access to safe abortion is a key part of women´s sexual and reproductive health and rights (SRHR) and essential to combat maternal
morbidity and mortality. The 2015 UN Sustainable Development Goals (SDGs) include a call for universal access to family planning, but
the UN has yet to formally endorse the need of access to safe abortion. WHO, however, recognizes this as one of the four key
components in reducing maternal deaths. Simultaneously abortion rights are threatened in countries where legislation has previously
been relatively liberal, such as in the USA and in Eastern Europe.
Cross-border reproductive care
Globalization has enabled new ways of parenthood. Many countries have legal restrictions regarding the use of surrogacy, but the
practice is to a large extent unregulated. Legal restrictions in the home country of the commissioning parents can be overcome by going
abroad for treatment. The increased use of transnational surrogacy has raised legal issues regarding the determination of parenthood.
The method has also created a heated debate, with the main discourse portraying surrogacy as exploitation. Cross-border reproductive
care has become a multi-billion-dollar industry with many unsolved legal and ethical issues such as women’s right to use their bodies as
they choose and to be surrogates or (re)defining what family and motherhood means.
New challenges
The world is facing new challenges such as increasing rates of non-communicable diseases (NCDs), environmental toxicants and global
warming. NCDs account for 71% of global deaths and 85% of these are in low- and middle-resourcee countries. In 2016, 39% of women
and men aged 18 or over were overweight (WHO data). Maternal obesity and gestational diabetes are associated with long term
consequences for both the mother and her offspring. Pregnant women and their developing fetus are particularly susceptible to
exposure to chemical compounds and environmental toxicants. The offspring may face harmful long-term consequences due to unique
and time-sensitive developmental processes. Risks may be cumulative and reflect multiple types of exposure. The expression of disease
processes is very complex, and to show absolute cause and effect associations is difficult. Many global organizations including FIGO are
working to increase knowledge about NCDs and also the effects of environmental toxicants on reproductive health. Ensuring universal
access to SRH care services is a target 3.7 of the SDGs. Refugee and migrant women and children are at particular risk of being
forgotten in the global momentum to achieve this target.
Keywords: Contraception, female genital mutilation (FGM), maternal mortality, neonatal mortality, obstetric fistula, safe abortion, sexual
and reproductive health and rights (SRHR)
Test yourself
Click at NFOG-MCQ and then at chapter 1.
References
Literature
Bearak J, Popinchalk A, Ganatra B et al Unintended pregnancy and abortion by income, region, and the legal status of abortion:
estimates from a comprehensive model for 1990-2019. The Lancet Global Health July 22, 2020
Ganchimeg T, Ota E, Morisaki N et al Pregnancy and childbirth outcomes among adolescent mothers: a World Health Organization
multicountry study. BJOG 2014 Mar;121 Suppl 1:40-8
Lancet Maternal Health series 2016
Trends in Maternal Mortality 2000-2017 Estimates by WHO, UNICEF, UNFPA, World Bank Group and the United Nations Population
Division 19 Sep 2019.
Authors
Seija Grénman, MD, Professor emerita, Finland
Margit Steinholt, MD, Norway
Kristina Gemzell Danielsson, MD, PhD, Professor, Sweden
Birgitte Bruun Nielsen, MD, PhD, Denmark
Last edited 30.10.2020
Published by:
NFOG - Nordic Federation of Societies of Obstetrics and Gynecology
Ole Mogensen Department of Obstetrics and Gynecology - Aarhus University Hospital
8200 Århus N
Telephone: +45 30 71 45 62
[email protected]
Region Midtjylland
2. Normal pregnancy
Take home messages
Gravidity (G) refers to the number of times that a female has been pregnant.
Parity (P) refers to the number of times that a female carries a pregnancy to a viable stage (Gestational week 22+0).
Gestational age (GA) is the time span since start of last menstrual period (i.e. about 2 weeks before conception).
Term pregnancy refers to the period from week 37+0 to week 41+6 (about 85% of all pregnancies).
Placentation is a very complex and active process where the placenta partly invades the endometrium.
The maternal immune system is strictly regulated during pregnancy in order not to reject the semi-allogeneic fetus, and aberrations in
immune regulation may contribute to pregnancy complications.
Introduction
Pregnancy, also known as gestation, is the period where one or more fetuses with corresponding placentae develop inside the uterus of
a woman. A multiple pregnancy involves more than one fetus, such as with twins or triplets. A pregnancy may end in a live birth, a
spontaneous miscarriage, an induced abortion, or a stillbirth. Childbirth typically occurs around 40 weeks (280 days) from the start of the
last menstrual period (LMP), but the actual conception takes place about 2 weeks after the start of LMP. This means that the ordinary
gestational length is about nine months.
Women who do not have a “meaningful” last menstrual period with either irregular menstruations, became pregnant after cessation of
contraceptives, became pregnant after IVF etc, are given an estimated gestational based on the size of the uterus or much better based
on an ultrasound scanning.
Even if the last menstrual period is “meaningful”, it is the gestational age calculated from an early ultrasound that is used during the rest
of the pregnancy.
Table 1: Definitions (Click to enlarge)
The first trimester includes conception, which is when the sperm fertilizes the egg. This usually takes place in either fallopian tube
and then the fertilized egg passes down and attaches to the inside of the uterus, where it begins to form the embryo and placenta.
During the first trimester (Figure 1) all the organs of the fetus are formed, and during this period the possibility of miscarriage
(natural death of embryo or fetus) is at its highest.
The second trimester consists of a period of continued growth and development of the organs and of the fetus, and at the latter
part of this period (around 22-23 weeks) the fetus has matured sufficiently to be able to survive outside the womb.
The third trimester: The fetus continues to grow and the organs mature until birth.
Fertilization
Through an interplay of the hormones that, among others, include follicle-stimulating hormone (FSH) that stimulates development of
follicles in the ovary and oogenesis creates a mature egg cell, the female gamete. Fertilization is the event where the egg cell fuses with
the male gamete, spermatozoon. This process usually occurs in the ampullary part of the fallopian tube. After fertilization, the fused
product of the female and male gamete is referred to as a zygote or fertilized egg.
Pregnancy rates for sexual intercourse are highest during the menstrual cycle time from some 5 days before until 1 to 2 days after
ovulation. This is due to the fact that sperm can exist longer and survive up to 5 days in the female reproductive tract. The oocyte
has a much shorter time span which normally is between 12 to 24 hours.
Fertilization can also occur by assisted reproductive technology such as artificial insemination and in vitro fertilization. Subsequently the
fertilized egg develops into a blastocyst and is transported to the uterus for implantation, which is when the future fetus attaches to the
lining of the uterus. This occurs about a week after fertilization. If this process is disrupted the fertilized egg can get stuck in the fallopian
tube creating an extrauterine pregnancy.
Figure 2a (7 days) +b (12 days) +c (16 days): Implantation of blastocyst in the uterus (Click to magnify)
Implantation and placentation
Placentation means the formation and growth of the placenta inside the uterus. It occurs after the implantation of the blastocyst into the
uterine wall and involves the remodeling of blood vessels in order to supply the needed amount of blood. In humans, placentation starts
with implantation at around 6-7 days after fertilization (Figure 2a).
In the case of twins, dichorionic placentation refers to the presence of two placentas (in all dizygotic and some monozygotic twins).
Monochorionic placentation occurs when monozygotic twins develop with only one placenta and bears a higher risk of complications
during pregnancy.
Cells in the endometrial stroma of the uterus respond to the presence of the blastocyst and to the progesterone secreted by the corpus
luteum by differentiating into metabolically active secretory cells called decidual cells, this is termed the decidual reaction.
Placental development starts with the first contact of the outer shell of a developing blastocyst with the uterine mucosa and progresses
rapidly during invasion of the endometrium. This newly established contact zone of two organisms develops rapidly and continuously
during pregnancy and controls fetomaternal exchange of nutrients, gases, and waste substances. At this stage, the blastocyst consists
of an outer single layered epithelial cover, called the trophoblast, and of an inner cell mass, called the embryoblast. The trophoblast is the
direct precursor of the epithelial parts of the fetomaternal barrier of the placenta, whereas the embryoblast contributes placental
mesenchyme and the fetal vascular system. As soon as it attaches, the trophoblast starts to proliferate rapidly and differentiate in the
inner layer of cytotrophoblast and the outer layer of syncytiotrophoblast (Figure 2b and 2c).
To establish the circulation of maternal blood in the intervillous space in the placenta (Figure 3.), larger endometrial arteries (spiral
arteries) and veins also erode and become connected with the intervillous space. Due to the growth of the fetus a degree of physiologic
changes in uteroplacental arteries must take place as the uteroplacental arteries are independent of the vasomotor function of the
mother, and the mother cannot reduce the nutrient supply to the placenta without decreasing the nutrient supply to her own tissues.
Reduced physiologic vessel function, including reduced arterial dilatation and reduced intraarterial trophoblast invasion, are regularly
observed in pregnancies complicated by preeclampsia, hypertension of pregnancy, and/or fetal intrauterine growth restriction. By
general agreement, failure of adaptation of the uteroplacental arteries to pregnancy conditions and thus preeclampsia and IUGR are
thought to be closely related to impaired trophoblast invasion. However, several different hypotheses concerning the nature of this
impairment have been proposed. It is especially unclear how the disturbance of invasion—occurring primarily during the first trimester
of pregnancy—is connected to the development of the full clinical syndromes (IUGR, preeclampsia, or the combination of both) during
the second half of pregnancy.
Figure 3. Placental circulation (Click to magnify)
Human fetal development
Embryogenesis
The fertilized egg immediately starts to divide and after around 4-5 days, at the 8-cell-stage, it turns into what is called a blastocyst. The
outer part forms the trophoblast, while a smaller part develops into the actual embryo. At the beginning of the second week the
blastocyst is embedded in the endometrium and the trophoblast develops into the placenta as previously described. The inner cell mass
now contains two layers, the primary endoderm and primary ectoderm that together form the bilaminary embryonic disc (Figure 2b). The
endoderm evolves to the primary yolk sac while the ectoderm forms a thin layer of cells that migrate and subsequently becomes the
amniotic sac.
Table 2: Development of germ cell layers (Click to enlarge)
The heart is formed from the mesoderm and starts as a primitive cardiac tube that during weeks 5 to 8 transforms through a series of
twists from a single chamber to the final four chamber structure. Heartbeats usually can be seen from around day 22-23.
Figure 4: Stages of human fetal development (Click to magnify)
Continued fetal development
After the primary organogenesis the fetus grows very rapidly and the proportion of the different parts of the body changes so that the
head which in the beginning of pregnancy is about a third of the body but at birth is a fourth (Figure 4).
The brain and nervous system develop most intensely during week 10 to 20, where the nerve cells migrate from the inner parts out
towards the surface of the brain. This is followed by persistent growth of dendrites and axons and furthermore myelinization, but the
brain is not fully developed at birth but continues to mature for several years. The development of the nervous system is very much
