Lecture conception

Normal conception,
implantation and physiological
changes in pregnancy
Obstetrics & Gynaecology, UFS
Standardised lecture
Last update 2022

The journey with obstetrics begins with understanding the

basics of the human reproductive processes, which I am
sure that you have studied in physiology. Understanding
the physiological adaptations will allow you to understand
the basic principles of diagnosis of pregnancy, and enable
you to monitor the woman effectively during her journey
of producing new members of their family.
This will also provide you with understanding of areas that
may go wrong during this process and assist in the
diagnosis and management thereof.

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Lecture conception

After this lecture, you must be

able to
• Describe the fertilisation process
• Understand the route of embryo travel and
implantation
• Able to describe the main physiological
adaptations during pregnancy
• Describe how early pregnancy changes assist in
diagnosis of pregnancy

The aim of this lecture is to clarify aspects of knowledge

and to give you and understanding of the process of
fertilisation and subsequent implantation in a way you will
understand where pathology may cause problems. You
must also be knowledgeable of the normal physiological
adaptations during pregnancy to enable you to understand
processes during pregnancy and how you can use this
knowledge to identify and confirm a possible pregnancy.

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As we discussed in semester 5, there is cyclic physiological

changes to prepare the uterus for reproduction. You have
seen this diagram before illustrating the normal female
reproductive cycle where ovarian follicles develop to
release an ovum, and prepare the endometrium for
implanting a fertilised egg, and if there are no implantation
of a pregnancy, then the endometrium breaks down and is
released, and the process start all over again. You must
know this process as it also forms the basis of
understanding interventions to prevent pregnancy.

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Fertilisation
process
• Sperm - Ovum
interaction

For fertilisation to happen there need to be 2 sources of

genetic material available. An ovum released by the
woman and a sperm released by the male. Timing of
availability of these two sources is important to allow
fusion and resulting pregnancy.

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Fertilisation
• Acrosome enzymes
• Sperm enter oocyte
• 2nd Meiotic division
• Sperm membrane
fusion
• Chromosomal
rearrangement
• Mitotic division

The fertilisation process begins when there is an

interaction between the sperm and the ovum. Availability
of enzymes in the acrosome on the tip of the sperm allows
the sperm to penetrate the granulosa cells of the corona
radiata and the zona pellucidum and stimulate completion
of the 2nd meiotic division in the oocyte. The sperm
membrane fuses with the oocyte allowing the genetic
material in the sperm-head to be deposited into the
oocyte while the tail remains on the surface.

By now the male and female chromosomes rearrange in a

mitotic coil and nuclear material are exchanged. The
mitotic division takes place and forms a 2-cell embryo

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Lecture conception

Fertilisation normally takes place at the fimbrial-end of the

fallopian tube. The developing embrio then moves along the
fallopian tube and enters the uterine cavity around the blastocyst
stage, where the blastocyst then implants in the endometrium
prepared for this process. This happens about 6 days after
fertilisation.
You should note that, already at this stage, should there be any
reason to result in delay of the movement of the fertilised egg,
implantation may happen before it reaches the prepared
endometrium.

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Lecture conception

At this stage the embryo developed into a blastocyst that

have developed an internal cell mass with a blastocoele as
well as a lining of trophoblast encapsulated by the zonal
pellucida. The inner cell mass will eventually develop into
a placenta.

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The first step for the embryo to implant is to leave its shell - the zona pellucida.
This process is known as hatching. It consists of the breakage of the zona
pellucida and the exit of the embryo, (the inner cell mas and the trofo-ectoderm.
Approximately between day 5 and 6 of embryonic development, the fertilized
egg is positioned in the endometrial tissue and remains immobile in the acquired
position. This is called apposition. It only directs the embryonic pole (where the
inner cell mass is) towards the epithelium of the endometrium.
In this phase, so-called pinopods or projections of the endometrial cells that help
the blastocyst join at the junction with the endometrial epithelium. Pinopods
only appear during the implantation window and disappear approximately on
the 24th day of the cycle. This is the moment when the trofo-ectoderm cells
strongly bind to endometrial cells through adhesion molecules such as integrins,
L-selectins, proteoglycans, fibronectins, etc.
Invasion is the process where the cells of the trofo-ectoderm proliferate towards
the endometrium and thus manage to displace and replace the endometrial cells
This usually occurs from day 8-9 of embryonic development.
This eventually leads to complete invasion of the endometrial stroma by the
trophoblast, which becomes totally embedded in the endometrium

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Lecture conception

This slide demonstrate how the embryo invaded the

endometrial stroma with development of a protective
decidual layer. I will not expect you to understand the
complex enzymatic reactions that occur as part of this
process.
There is however a number of important hormonal
changes that happen that you must understand.

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Lecture conception

Key hormones

• Human gonadotropin (HCG)

• Progesterone
• Oestrogen

HCG is produced by the placenta after implantation- It

supports the maintenance functioning of the corpus
luteum.
Progesterone help to establish the placenta and
stimulates growth of blood vessels supplying the womb. It
also inhibits contractions of the uterus and strengthen the
pelvic muscles. Initially it is produced by the corpus
luteum, but this function is taken over by the placenta
after about week 10 of the pregnancy

Estrogen during pregnancy is mainly produced by the

placenta.

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HCG

This diagram illustrates the trends in hormonal blood

concentrations throughout pregnancy.
Human chorionic gonadotropin is produced by the trophoblast in
very early pregnancy- the Betha fraction can be detected in
maternal serum already by 8-11 days and detectable levels by the
time the first day of the period is missed. It stimulates the corpus
luteum to adequately produce oestrogen and progesterone until
the placenta is sufficiently advanced to take over this function at
around 6-7 weeks of gestation.
Other effects during pregnancy includes regulation of oestrogen
production and suppression of maternal immunological effects of
the fetus.
Concentrations of Estrogen and progesterone continue to rise
throughout the pregnancy.

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HORMONE ORIGIN FUNCTION

HCG trophoblast Stimulate corpus luteum
Regulation of oestrogen production
Immunosuppression
Progesteron Corpus luteum Decrease smooth muscle tone (uterus, ureter, stomach)
e syncytotrophoblas Slight increase in basal temperature
t Impact on brain – sensation of need for rest

Oestrogen Placenta-fetal unit Rapid increase first trimester- nausea

(Various) Promote placental angiogenesis & uterine artery vasodilatation
Hygroscopic tissue
HPL syncytotrophoblas Promote energy supply to fetus
t Decrease maternal insulin sensitivity and decrease maternal glucose
utilisation
Potent agonist of the prolactin receptors
promotes ductal and alveolar growth in the mammary gland
Relaxin Ovary Prepare endometrium to establish pregnancy
Placenta Transform endometrium into decidua
Stimulate secretion of various hormones
Facilitate softening and ripening of the cervix
Prolactin Endometrial Regulate amniotic fluid osmolarity
decidua Stimulate fetal alveolar cells to produce surfactant
Prepare breasts for lactation

Besides HCG, progesterone and oestrogen, there are other

hormones to take note of. You need to note that for some
hormones the fetus and the placenta are combined
responsible for production. Although the detail of the
hormonal synthesis and functions is complex, the detail
will not assist in your basic understanding of the subject.
You should however be able to explain the core functions
of these 6 hormones in pregnancy

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Other Adaptations in pregnancy

• Pregnancy affects various physiological systems
to the extent that it simulates temporarily a
different specie
• Knowledge of these differences are important to
understand behaviour and physiological
responses

There are a wide range of physiological adaptations

occurring during pregnancy due to either hormonal
influence, or the physical impact of the enlarging
pregnancy. You need to understand that these changes
may be different from what you have learned about
normal human physiology. As a medical practitioner you
need to know these physiological changes as it may impact
on your diagnostic capacity during pregnancy and
credibility on advice and management of disease during
pregnancy.
We will tackle these adaptations in a systematic and logic
way.

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Lecture conception

THYROID

Commencing early in the pregnancy, there is a sharp rise in

thyroxin until it reach a plateau around 10 weeks which is
maintained until after delivery. This must not be confused
with hyperthyroidism. There is also a similar increase in
the thyroid binding globulin. Although the concentrations
of thyroxin measures high, the free available thyroxin is
not appreciably higher than in the non-pregnant
individual. The thyroid may increase slightly in size during
pregnancy, but not enough for a clinician to detect.

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Lecture conception

INSULIN

• Hormonal effects
• Insulin resistance

The developing fetus creates an increasing nutrient

demand on maternal metabolism and homeostasis.
During pregnancy there is an increase in the pancreas beta
cell mass through proliferation and hypertrophy. In a
normal pregnancy maternal tissues become increasingly
insensitive to insulin under the influence of placental
hormones to divert more glucose to the feto-placental
unit. As glucose gets prioritized for fetal utilization
through reduced uptake by maternal tissues, lipolysis
increases during pregnancy allowing for fatty acids to be
used as an energy fuel for the mother. The combination of
decreased insulin sensitivity and increased insulin
secretion maintains relatively normal glucose levels in late
pregnancy.

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Hormonal influence affect the insulin metabolism and force

pregnancy in a state of insulin resistance.

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Cardiovascular

• Heart rate ↑
• Pulse volume ↑
• Cardiac output ↑
• Systemic vascular
resistance↓

Pregnancy is associated with vasodilation of the systemic vasculature and the

maternal kidneys. The systemic vasodilation of pregnancy occurs as early as at 5
weeks and therefore precedes full placentation.
There is substantial activation of the renin-angiotensin-aldosterone system in
normal pregnancy, with increases in plasma volume starting at 6-8 weeks and
rising progressively to 30 weeks

In the first trimester there is a substantial decrease in peripheral vascular

resistance, which decreases to a nadir during the middle of the second trimester
with a subsequent plateau or slight increase for the remainder of the pregnancy
The cardiac output increases throughout pregnancy. This is to accommodate the
increase in blood volume.
The heart rate increases during the gestation and reach a maximum change
during the second trimester – and increase of 10-20 bpm above the non-
pregnant values.
.

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Lecture conception

There is a noticable decrease in arterial pressures, including systolic blood

pressure (SBP) and diastolic blood pressure (DBP). The decrease occurs early in
pregnancy (6- to 8-week gestational age) compared with preconception values.
This is probably associated with the hormone relaxin. Arterial pressures begin to
increase during the third trimester and return close to preconception levels
during the postpartum period.

Increase in the cardiac output is largely due to an increase in the stroke volume.

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Lecture conception

Heart

The increase in cardiac output may cause a physiological

murmur audible in the heart and most women may
develop a 3rd heart sound

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Lecture conception

Respiratory

• Respiratory
• Ventilation rate↑
• Respiratory volume↑
• Total lung capacity ↓
• Pulmonary vascular resistance
↓

The respiratory system is affected by both mechanical

changes and the physiological alteration of hormonal
patterns. Progesterone acts as a trigger for the primary
respiratory centre by increasing the sensitivity of the
respiratory centre to carbon dioxide. It also alters the
muscle tone of the airways resulting in a bronchodilator
effect. It also mediates hyperaemia and oedema of the
mucosal surface resulting in nasal congestion.
The increase in uterus size in later pregnancy results in
elevation of the diaphragm, and altered thoracic
configuration causes a reduction of the residual capacity
and expiratory reserve volume- other dimensions increase
to minimise the impact of a decrease in the total lung
capacity.

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Lecture conception

This slide illustrates the changes throughout pregnancy.

Around 70% of pregnant women may experience some
dyspnoea ( or sensation of breathlessness) during their
daily activities starting from the first trimester. Such an
early onset excludes mechanical changes as a cause – this
sensation is probably due to an increased awareness of the
new sensation of hyperventilation.
The decrease in reserve capacity does not affect the
normal pregnant woman, but may have serious
consequences with underlying lung pathology or disease
with increased respiratory demand

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Lecture conception

Gastro-intestinal

• Reflux ↑
• Ph↑
• Higher empty time
• Peristalsis↓

Changes in the gastrointestinal (GI) system during pregnancy are caused by the
enlarging uterus and hormonal changes of pregnancy. Anatomically, the intestine
and stomach are pushed up from their original positions by the enlarging uterus.
While there aren't any intrinsic changes in the sizes of the GI organs, the portal
vein increases in size due to the hyperdynamic state of pregnancy. Elevated levels
of progesterone and estrogen mediate most of the functional changes of the GI
system during pregnancy. Progesterone causes smooth muscle relaxation which
slows down GI motility and decreases lower esophageal sphincter (LES) tone. The
resulting increase in intragastric pressure combined with lower LES tone leads to
the gastroesophageal reflux commonly experienced during pregnancy.

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Lecture conception

Renal changes

• Glomerular filtration rate ↑

• Kidney size↑
• Altered tubal reabsorption
• protein, glucose, amino acid
• Alter electrolyte balance
• Increase plasma volume

Pregnancy requires major changes in the structure and

function of the kidney.
Because of changes in the vascular and interstitial spaces ,
the kidneys normally increase in size by up to 30% (1-1,5
cm). Due to the increased cardiac output , renal plasma
flow and glomerular filtration rate (GFR) increases (by
about 40%)

In early pregnancy renal plasma flow (RPF) exceeds GFR

and, as such, filtration fraction is slightly lower than in
nonpregnant controls. This changes some-time between
week 12 and the third trimester, in which RPF falls toward
nonpregnant levels, whereas GFR continues to be

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Lecture conception

elevated, resulting in an increased filtration fraction. All

these values normalize 4–6 weeks after delivery
Angiotensin levels increase throughout pregnancy due to
increase in renin substrate production under the influence
of estrogen.
The angiotensin maintains blood pressure and helps to
retain salt and water in pregnancy as maternal systemic
and renal arterial dilation (with resulting salt and water
loss) creates an “underfilled” cardiovascular system.
During the second and third trimesters, there is an increase
in exchangeable sodium. Furthermore, during pregnancy,
relaxin stimulates increased vasopressin secretion and
drinking, resulting in increased water retention. Despite
increases in exchangeable sodium, plasma osmolality is
reduced and the hyponatremic hypervolemia of pregnancy
ensues.
Progesterone is a potent aldosterone antagonist that acts
on the mineralocorticoid receptor to prevent sodium
retention and to protect against hypokalemia. The
importance of aldosterone is evident in preeclampsia in
which plasma volume is reduced and aldosterone
concentrations are low. Activation of the mineralocorticoid
receptor by maternal aldosterone appears to be required
for trophoblast growth and normal fetoplacental function.
Maternal plasma atrial-natriuretic peptide levels increase
by 40% in the third trimester and are 1½ times higher than
normal in the first week postpartum, suggesting a
significant role in postpartum diuresis.

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Lecture conception

Genital changes

• Size and form of

uterus
• Cervical changes
• Softening
• Discoloration
• Mucus discharge
• Pressure on the
bladder

The uterus enlarges substantially during pregnancy and changes from a pelvic to
an abdominal organ. This increase results in pressure on the bladder creating the
sensation of fullness.
The uterine cervix is a remarkable structure, which plays an important role in
pregnancy. During the development of the baby within the uterus, the cervix
usually remains firmly closed to ensure that the developing fetus attains an
appropriate degree of maturity to permit extra-uterine survival. On the other
hand, it prepares for labour and birth, by undergoing a process of effacement,
whereby the substance of the cervix shortens and thins out. During labour, it
must be stretched and dilated to a sufficient diameter, usually about 10cm at
term, to allow the successful passage of the fetus through the birth canal
During pregnancy there is an increase in the blood supply to the vagina, its colour
change from pink to purple, and becomes more elastic in the second trimester

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Breasts

• Proliferation of secretory
tissue
• Lobular hyperplasia
• Galactorrhoea
• Increase in size

Under the influence of estrogen there is proliferation of the mammary ducts, as

well as, to a lesser degree, alveolar-lobular growth. This begins already in the first
trimester of pregnancy

Gradual expansion of the glandular tissue in the breast results in invasion of the
adipose tissue and simultaneous increase in vascularity and blood flow.
During the second and third trimesters, progesterone induces lobular
hyperplasia, as well as the continuous involution of the fibrofatty stroma.
Although the greatest breast growth occurs up to week 22 of pregnancy,
considerable growth can occur in the last trimester and postpartum period in
some women.

During pregnancy, the breast undergoes both anatomic and physiologic changes
to prepare for lactation. During the first trimester, the ductal system expands and
branches out into the adipose tissue in response to the increase of estrogen.
Elevated levels of estrogen also cause a decrease in adipose tissue and ductal
proliferation and elongation. Estrogen also stimulates the pituitary gland which
leads to elevated levels of prolactin. By the twentieth week of gestation,
mammary glands are sufficiently developed to produce components of milk due

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to prolactin stimulation. Milk production is inhibited by high estrogen and

progesterone levels and colostrum is produced during this time. In the third
trimester and then rapidly after birth, these levels decrease, allowing for milk
production and eventual let-down to allow for breastfeeding.

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Lecture conception

Haematological

• Increased plasma volume

• Hyper-coagulability
• Immunological
adaptations

I have previously alluded to the increase in blood volume, but it is important to

note that the increase in the plasma volume is greater than the increase in the
red cell mass, resulting in a lower recorded haemoglobin referred to as a
physiological Anaemia.

Most changes in blood coagulation and fibrinolysis create

a state of hypercoagulability. This phenomenon protects
the woman from haemorrhage during delivery but
predisposes her to thromboembolism both during
pregnancy and in puerperium. This is as a consequence of
increased coagulation factors and a decreased fibrinolysis.
The increase in clotting activity at the time of delivery is
most likely related to expulsion of the placenta and release
of thromboplastic substances at the site of separation.

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There are also immunological adaptations to prevent

rejection of the developing fetus.

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Musculoskeletal
• Mechanical Gait
changes
• Relaxed ligaments
• Leg cramps

The increased lordosis of pregnancy combined with the effects of Relaxin on the
joints of the pelvis and the weight of the gravid uterus with resultant anterior
shift in the center-of-gravity all contributes to complaints of low back pain in the
patient who is pregnant.
Relaxin and progesterone allow the joints of the pelvis to become more flexible
during pregnancy as the mother's body prepares for the delivery of the baby. This
increased laxity may cause pain in the sacroiliac joint or at the pubic symphysis in
some women. Changes in the width of the pubic symphysis probably occurs in all
pregnant women and the maximum widening considered nonpathological is 10
mm.
Leg cramps are another common musculoskeletal complaint during pregnancy
affecting between 15% and 30% of women. These cramps usually occur during
the second half of pregnancy, most often affecting the muscles of the calf and
occurring at night approximately 75% of the time. The cramps are described as
forceful tetanic contractions that often wake the woman from a sound sleep. The
exact aetiology of leg cramps during pregnancy is unknown but they may be
caused by a magnesium or calcium deficiency.

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Skin changes

• Pigmentation
• Hyperpigmentation
• Melasma
• Stria gravidarum
• Pruritus
• Vascular
• Spider angiomas
• Palmar erythema
• Varicosities
• Non-pitting oedema

Physiologic skin changes are common during pregnancy due to a temporary shift
in hormonal, metabolic, and immunologic factors. Physicians may mistake
normal skin changes in pregnancy as pathologic change within the skin, and so
an appreciation of the common and less common skin manifestations will assist
in appropriate patient care.
Listed here is the common changes seen during pregnancy

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Here are some hyperpigmentation examples,

demonstrating pigmentation of the linia alba in the first
pregnancy to form the linea nigra- a dark line in the middle
of the abdomen.

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Dark grey-brown skin pigmentation predominantly in the

face is called melasma – in your text book this may be
described as chloasma. This is triggered by increased levels
of hormones, especially during the latter part of the
pregnancy. It is sometimes called the “face mask” of
pregnancy. It cannot be prevented but can be less
prominent if exposure to sunlight is avoided. It is present
in 50-70% of pregnant women.

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During the first pregnancy the areola also change from a

pink colour to a darker pigmented brown

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The abdominal skin stretches in many ways to

accommodate the growing baby– this can result in stretch
marks called stria gravidarum. After delivery the skin does
not normalise and scar tissue may form instead. It can also
be noticed in the breasts, thighs and lower back.

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Palmar erythema is the red colouring of the palms and

occurs in 30% of pregnancies and my be associated with
the increased oestrogen production. Estrogen is also
thought to play a role in other vascular changes such as
development of the spider angiomas.

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Lecture conception

Varicose veins can occur in many areas and are aggravated

by mechanical pressures, especially to the lower limbs

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DIAGNOSIS OF PREGNANCY

• CLINICAL Signs & Symptoms

• Diagnostic tests

Knowledge of these physiological changes should allow

you to be able to make the diagnosis of pregnancy.
The diagnosis would be based on a combination of
symptoms that you can extract from the history, and the
physical signs that you can observe with the clinical
assessment.
The pregnancy can also be confirmed with a biochemical
based diagnostic test

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SYMPTOMS
• Amenorrhoea ( Missed a • Food cravings
period) • Mood swings
• Light spotting • Constipation
(implantation bleeding)
• Bloating
• Elevated basal
temperature • Heartburn
• Nausea/vomiting • Headaches/dizziness
• Swollen (tender)breasts • Fatigue
• Urinary frequency

The following symptoms are common already in early

pregnancy and in combination of a few be able to direct
you in thinking of pregnancy. Women with an implantation
bleed or whom experienced irregular menstruation may
not be aware of missing a period.

Some physiological changes results in complaints that is

often referred to as minor complaints during pregnancy.

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Signs Early pregnancy

• Breasts
• Galactorhoea
• Cervix
• Softening (Hegar)
• Mucus changes
• Blue hue (chadwick
sign)
• Hegar’s sign

Late in pregnancy a pregnant uterus is palpable in the

abdomen and the suspicion of pregnancy is easy.

In early pregnancy you need to be alerted by some specific

clinical signs

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Chadwick’s sign

Chadwick sign is a bluish discoloration of the cervix, vagina, and labia resulting
from increased blood flow. It can be observed with a speculum examination as
early as 6 to 8 weeks after conception, and its presence is an early sign of
pregnancy.

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Hegar’s Sign

Hegar’s sign is softening of the isthmus of the uterus – this

is best seen around 8-9 weeks gestation and can become
so soft that the examiners fingers can almost get together.
This can be palpated during a bimanual pelvic examination
assessing the characteristics of the uterus.

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Vaginal discharge

A clear or milky-white discharge is normal in pregnancy

and can start within 2 weeks of conception – even before
she missed a period. It is usually thin, milky white and
stretchy – similar to the consistency of egg white

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DIAGNOSTIC TESTS
• Based on the presence of BHCG

The diagnostic tests are based on the beta chain of the

human choriogonadotropin as this is produced by
pregnancy and there is a sharp increase already early in
the pregnancy. Levels are sufficiently increased to
diagnose the pregnancy already by the time she missed
her next period. This can be performed as an agglutination
test but…

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Modern products does not require any technical skills and

is now freely available also to the public.
Alternatively the laboratory can perform a quantitively
assessment on serum for HCG.
The modern urinary pregnancy tests are sensitive and
reliable.
Once pregnancy is confirmed, the woman need to attend
antenatal assessment and follow-up to ensure a healthy
mother and baby

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TAKE HOME
• Pregnancy results in various
physiological changes during pregnancy
• Some changes results in signs and
symptoms that will allow diagnosis of
pregnancy
• Some changes may be experienced by
the pregnant woman as abnormal and is
regarded as minor complaints during
pregnancy

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