Alterations in Reproduction

Terminology
- HPO axis
- Hypothalamic pituitary ovarian axis, the main hormonal feedback pathway
responsible for the reproductive system
- Menarche
- 1st menstrual cycle achieved
- Os
- Opening from the uterus through the cervix into the vagina, can measure the
dilation of the os to monitor the progress of labour
- Fundus
- The top of the uterus
- During pregnancy à Measuring point for monitoring growth of the fetus
(symphysis-fundal height)
- After delivery à palpated to monitor the resolution phase
- Infertility
- Failure to achieve pregnancy after one year of unprotected intercourse, noting
that if the female partner is over 35 years then the interval is shortened to 6
months
- IVF
- In vitro fertilization
- Process by which ova and semen are collected from the individuals and mixed
together to permit fertilization to occur after 3-5 days later 1-2 growing embryos
are returned to the uterus, any remaining fertilized ova can be frozen for future
attempts
- Parity
- Number of deliveries that a women has had over 20 weeks gestation
- When this number is over 5, this is considered to be a state of grand multiparity,
or the woman is referred to as grand multipara
- GTPAL
- Obstetrical history
- Gravida à total number of pregnancies – including miscarriages, abortions, and
stillbirths
- Term à total # of deliveries over 37 weeks gestational age
- Preterm à total # of deliveries between 20- and 37-weeks gestational age
- Abortions à spontaneous or therapeutic (surgical intervention)
- Living Children à # of living children
- Viability
- Point at which, should a fetus deliver, there is a reasonable expectation of
survival, usually defined as 500 gm or more than 20 weeks’ gestation
- Macrosomia
- Fetal head size has grown larger than can be passed vaginally
- Large at birth

REPRODUCTION 1
 - Polyhydramnios
- Amount of amniotic fluid is more than 2 standard deviations above the norm for
gestational age

Normal Female Anatomy

- Sexual differentiation of an embryo occurs around the 7th week of gestation;
determined by the sex chromosome -XX (female), XY (male)
- SRY protein on the male or Y chromosome is the testes determining factor
- In females, w/o exposure to this protein, will develop the vagina, uterus, and
fallopian tubes otherwise known as Mullerian ducts.
- Ovaries produce secondary oocytes and estrogen, progesterone, inhibin and relaxin
- At birth, the ovaries of the female newborn contain all their primary oocytes and
secondary oocytes are formed after puberty once a month at ovulation
- Uterine tubes/fallopian tubes à transport the secondary oocyte to the uterus and
normally these tubes are the sites where fertilization occurs
- Uterus à site of implantation for the fertilised ovum; where fetus will develop during
pregnancy and will promote the progression of labour; endometrium, myometrium,
perimetrium
- Vagina à receptacle for sperm during intercourse, passageway for childbirth
- Routine pelvic exam à palpate uterus during a bimanual exam to determine the
uterine lie or position
- Position of uterus in the pelvis are something females are born with, will remain
the same throughout

Female Hormones

REPRODUCTION 2
GnRH
- Gonadotrophin releasing hormone
- Binds to gonadotrophs in the anterior pituitary glands and stimulates them to increase
secretion of FSH and LH
FSH
- Stimulates growth of follicles of the ovaries to produce estrogen, progesterone, and
inhibin

LH
- Stimulates ovulation, remembering the LH surge and the formation of corpus luteum
Estrogen
- Development and maintenance of the female reproductive structures and secondary
female characteristics: adipose tissue deposition, voice pitch, broad pelvis and hair
growth pattern
- Lowers blood cholesterol – unknown mechanism
Progesterone
- Secreted mainly by corpus luteum in the last two weeks of menstrual cycle
- Works with estrogen to prepare and maintain the endometrium, and to prepare
mammary glands for lactation
Relaxin
- Produced by corpeus luteum
- Role in uterine smooth muscle relaxation
Inhibin
- Secreted by granulosa cells
- Work with estrogen and progesterone to provide feedback for the HPO axis
- Either stimulate or inhibit further release of FSH and LH

REPRODUCTION 3
Female Monthly Cycle Summary

- Normal female reproductive cycle à 24 to 36 days à biggest variation occurs during

pre-ovulatory phase
- Day 1 – 5
- Menstrual phase when the uterus sheds all but the deepest layers of
endometrium (approx. 50-150 mL of blood, tissue, fluid, mucus, and epithelial
cells
- Discharge d/t the decreased amount of progesterone and estrogen
- Oral birth control pills (exogenous hormones) à manipulate menstrual cycle;
when woman stops taking, progesterone levels decreases and promotes
bleeding
- Ovarian hormones are at the lowest levels and this stimulates the secretion of
GnRH and subsequently FSH and LH
- Day 6 – 14
- Variable pre-ovulatory phase
- Under influence of FSH, maturation of dominant follicle occurs
- Proliferative phase of the uterus as estrogen promotes endometrial growth
- ~ Day 14, ovulation occurs when the secondary oocyte is released into the
pelvic cavity surrounded by the zona pelucida and corona radiata

REPRODUCTION 4
 - Left over cells in the ovary become the corpus luteum under the influence of LH
then secretes estrogen, progesterone, inhibin and relaxin
- Day 15 – 28
- Post-ovulatory phase
- Progesterone and estrogen secreted by corpus luteum causes further growth
and coiling of endometrial glands and thickening of the endometrium à all in
prep for a fertilized ovum
- w/o fertilized ovum, corpus luteum degenerates, leading to a decreased
amount of progesterone à menstruation occurs

Implantation
- Zygote àfertilized egg
- Blastocyst à collection of rapidly proliferating cells ~2 weeks
- Embryo à 2-8 weeks
- Fetus à 8 weeks to birth
- To achieve pregnancy, fertilized zygote must penetrate endometrial layer of uterus
- Day 10-12 post-fertilization à rise in beta-subunit of glycoprotein (hCG)
- hCG à marker detected in urine and blood, produced by trophoblast, role is to
maintain the corpus luteum which produces the increasing amount of progesterone
needed to support and thicken the uterine lining
- Insufficient levels of hCG causes corpus luteum to regress, progesterone levels will
drop, and sloughing of endometrium will occur aka menstruation
- Beta-hCG doubles every two days in early pregnancy à support viability of
pregnancy or rule out ectopic pregnancy
- Blood test more sensitive à can detect a rise above 5 iu/l
- Urine test à 25 iu/l; home pregnancy test à 1st void in the morning, hormones most
concentrated

Development
- End of 13th week of gestation, all major structures and pathways are formed,
remainder of pregnancy more about growth and fine-tuning; why 1st trimester is most
important
- time when developing fetus could be exposed to alcohol, recreational drugs,
smoking
- Chorion membrane à derived from inner layer from ectoderm that becomes the
trophoblast and the outer layer is mesoderm
- trophoblast divide rapidly and creates small finger-like projections to the uterine
myometrium to begin to form the chorionic villi
- mesoderm fills in projections with branches of umbilical vessels so they can be
vascularized
- Chorion à contributes to the dev’t of placenta, esp those that are in contact with the
uterine wall
- Between 8 to 10 weeks, placenta will develop and take over in producing
progesterone and hCG, enabling the corpus luteum to degenerate

REPRODUCTION 5
 - At 10-14 weeks, chorionic villi and intervillous spaces or maternal sinuses has blood
flowing and can facilitate nutrient and gas exchange
- O2 plays a role in regulation of villous vasculogenesis
- There is increased blood flow, increased oxygen tension that may contribute to
oxidative stress which can be overwhelming in some pregnancies, can lead to
miscarriage
- Arteries and veins increase in number & capacity; divide into secondary then tertiary
vessels before entering the mainstem villi or umbilical stalk

Placental development

- Placenta provides all fetal nutrition during pregnancy

- Formed by the 10th week of gestation
- Acts to filter nutrients, oxygen, and fetal waste products by diffusion between
the mother and the fetus
- Forms finger-like projections or interdigitations into the endometrium that
performs these important functions
- Lochia flow à occurs after delivery of baby, sign that location of placenta is healing
- Amnion à membranous sac that surrounds the developing fetus and provides
protection as the fetus grows
- Appears as a small sac that eventually enlarges and becomes fluid filled by 4th
or 5th week
- Amniotic fluid or liquor continues to accumulate to be a total of about 1-2 litres
at term
- When water breaks, there is an opening on amniotic sac that permits the fluid to exit
- Note color and quantity of fluid to determine if fetus had passed meconium
prior to birth – this changes delivery protocol (institution-specific)

REPRODUCTION 6
 - Polyhydramnious
- associated with gestational diabetes (GDM); increased thirst, frequent urination,
too much fluid
§ involves excessive amount of fluid,
- can overextend cavity, can lead to poor descent of presenting part into pelvis
- if membrane ruptures prior to descent, potential prolapse of umbilical cord à
medical emergency
- Gestational HTN
- Oligohydramnious or too little fluid around the baby
- Can lead to intolerances of the stresses of labour i.e. fetal heart decelerations
§ High blood pressure à vessels constricted à not as much blood passes
b/w placenta and fetus à results in lower fluid volume

Placenta
- Two umbilical arteries, one umbilical vein
- Umbilical veins carry oxygenated blood to the fetus while the umbilical arteries
remove deoxygenated blood
- Pulmonary artery carries deox blood to lungs, pulmonary veins return ox blood to
heart
- Delivery of placenta à 3rd stage of labour
- Cord is always inspected after delivery for presence of three vessels, as well as during
U/S
- Inspected during delivery by midwife or physician to ensure it is whole and there are
no gross abnormality
- Velamentous or circumvallate cord insertion
§ Major umbilical vessels separate in the fetal membranes before reaching
placental disk
§ No major consequence in utero, but can lead to a greater chance for
cord trauma with bleeding during delivery
- Vasa previa
§ Placenta after delivery are running unprotected through the membranes
- Succenturiate or accessory lobe of placenta
- Placenta accreta
§ Results from a lack of formation of a normal decidual plate
§ Chorionic villi extend into myometrium, placenta cannot separate
normally following delivery
§ Sever hemorrhage results
- Sent to pathology for histological studies if:
- Baby is small for gestational age (<2500 grams at full term birth)
- Post-dates – born after 41 completed weeks of gestation
- Placenta does not appear normal on gross examination

REPRODUCTION 7
Placental Positions

- Where placenta develops happens by chance

- Risk factors for dev’t of placenta previa
- Grand multiparity
- Recurrent abortions/miscarriages
- Uterine surgery
- Placenta Previa
- Condition whereby the placenta forms so it is either completely or partially
covering the uterine os
- Always commented on during antenatal U/S
- Done at 18 to 20 weeks of gestational age
- Abnormal finding placentation
- Measure how close the leading edge of the placenta is to the uterine os, which
is the opening of the uterus to the cervix
- Provides guide for delivery options
- Potential that position can change as uterus grows hence repeat U/S will be done
- If placenta completely covers os à CS delivery
- Low-lying or marginal previa à may consider vaginal delivery w/ double setup
- Big risk: antepartum hemorrhage
- Complete pelvic rest

REPRODUCTION 8
Hormones in Pregnancy

- Most important à rise in estrogen and progesterone and appearance of hCG and
placental proteins
- hCG à initially created by trophoblast; main role to maintain corpus luteum of
pregnancy
- has TSH-like activity, stimulate maternal thyroid gland to increase circulating
thyroid hormones
- Thyroxin à crosses placenta and facilitate fetal development
- thyroid dysfunction can be linked to preeclampsia, gestational HTN, low birth
weight, preterm delivery, perinatal morbidity and mortality.
- Human chorionic somatomammotropin (hCS)
- Similar to pituitary growth hormone
- Aka human placental lactogen
- Growth hormone of pregnancy
- Anti-insulin (decrease glucose uptake, increase free fatty acids being released)
- Potent prolactin-like or lactinogenic bioactivity
- Secreted by placenta into maternal circulation, little reaches fetal circulation
- Human chorionic corticotropin (hCC)
- Can be detected in both maternal and fetal circulations
- Maternal ACTH does not reach fetus
- PAPPA à used for Down syndrome screening
- Corticotropin releasing factor (CRH)
- 100 picomoles per litre in 3rd trimester
- 500 picomoles per litre in the last 5 to 6 weeks of gestation
- Can rise two or three-fold with onset of labour

REPRODUCTION 9
 - Major role in parturition
§ With increased CRH near the end of pregnancy, smooth muscles are
relaxing, and prostaglandin formation is increased
- Fetal lung maturation and fetal surfactant
§ Cortisol signals lungs to start producing surfactants (functioning tissus)
§ Lungs don’t function in-utero
§ Celestone or Bethamethasone à corticosteroid
• 2 doses, 12 to 24 hours apart (IM)
• Mimic effects of natural cortisol & promote lung maturation
- Placental progesterone
- Maintain pregnancy, especially uterine linings
- Estrogen
- Primarily formed from DHEA – w/ci s secreted by zona reticularis of adrenal
cortex of both mom and fetus (larger quantities)
- Transported to placenta where it is converted to estradiol, estrone, and estriol
- Causes enlargement of uterus, breast ductal structure, and the pregnant
woman’s eternal genitalia
- Works with relaxin to relax the pelvic ligaments (symphysis pubis) and become
elastic to allow for easier passage of fetus during delivery
- Human Chorionic Gonadotropin
- Alpha and beta subunits;
§ beta unit measured with pregnancy tests of blood & urine
§ alpha unit fertility treatments to promote ovulation
- Estrogen & Progesterone
- Continue to rise during pregnancy
- Support changes in the breast tissue to permit breast feeding and to keep the
endometrial lining thick and plentiful to support the utero-placental unit

REPRODUCTION 10
Changes in Pregnancy

- 12 weeks’ gestation
- begin to palpate uterus above the pelvic bone while doing a pelvic exam
- may be able to ascultate the fetal heartbeat with U/S doppler
- shape of a large avocado or the size of a softball
- 16 weeks
- Fundus of uterus is about halfway b/w pubic bone and umbilicus
- 20 weeks
- Fundus is around umbilicus
- Start to measure symphysis-fundal height (SFH)
- Singleton pregnancy
§ SFH within 1 to 2 cm of the number of weeks pregnant
- NOTE:
- Pre-term à Infant born before 37 weeks
- Term à born b/w 37 and 42 weeks
- Post-term à born after 42 weeks
- Weight gain
- Nutrient needs will increase later in pregnancy, not in the early stages
- Excessive weight gain à gestational DM, gestational HTN, fetal macrosomnia
- Dystocic labour à where uterus cant get into a concerted, rhythmic pattern of
contractions to affect delivery; labour can be augmented
- Dating for Expected Date of Confinement
- Use first day of last menstrual cycle; interval from last menses to ovulation is
included in EDC calculation
- Naegele’s rule
- Subtract 3 months and add 7 days to first day of LMP

REPRODUCTION 11
Full Term Pregnancy
- Try and evaluate presenting position of the fetus in the pelvis
- Palpate anterior and posterior fontanelles of infant during a vaginal exam
- Anterior fontanelle à diamond-shaped soft spot created where the skull bones
come together
- Posterior fontanelle à triangle-shaped
- Purpose of determining fontanelles à determine which way occiput is pointing
§ Occiput anterior à best position for vaginal delivery
§ Occiput transvers and posterior position à wide part of hair to narrow part
of pelvis à failure to progress
- Uterus
- Enlarges from 50 gm to 1100 gms and volume increases from 10 mL to hold an
average of 5,000 mL or 5 L and in some extreme cases up to 20 L.
- More spherical by 12 weeks
- Increase length compared to width at the rest of pregnancy
- Starts in pelvic cavity but after 12 weeks, rises towards the anterior abdominal
wall and ultimately the liver and starts to displace intestines laterally and
superiorly
- Hypertropic uterus à more elastic and fibrous in response to estrogen and
progesterone levels
- Position of placenta influences where the uterus becomes more hypertropic
because the area of the placenta site enlarges more rapidly than the rest
- Hegar’s sign à uterine isthmus becomes soft and compressible
- Breast
- Nipple enlargement and increased pigmentation
§ W/ increased blood supply, the veins become more visible
§ 3rd trimester à the proliferation of mammary glands occurs r/t pregnancy
hormones
- Glands of Montgomery à more pronounced elevations noted on areola
(hypetropic sebaceous glands)
- Mammary glands ready for lactation, but is prevented with high levels of
estrogen
§ Resumes after delivery, when estrogen levels drop
- Cardiovascular
- Uterus enlarges and pushes against diaphragm
- Heart becomes laterally displaced to the left, impacts PMI landmark
- Mother’s CO increases 30-40% and peaks at around 24 weeks
- Blood volume increases 40-50% during pregnancy; this hypervolemia helps meet
metabolic demands pf placenta and enlarging uterus
- There is a disproportional increase in plasma compared to erythrocytes that can
lead to a physiological anemia of pregnancy
- Higher blood volume à accounted for by increase in circulating aldosterone
(promotes water retention in kidney) & increased bone marrow RBC production
and reticulocytes being released due to higher maternal erythropoietin levels
- Systolic ejection murmur

REPRODUCTION 12
 - SBP and DBP decline slightly during pregnancy; reach pre-pregnancy levels by
approximately 36 weeks
- Venous pressure increases later in pregnancy – lower extremities à lead to
venous congestion in the form of varicose veins, hemorrhoids, and dependent
edema
- Respiratory
- Remains unchanged
- Tidal volume and resting minute ventilation increase
- Functional residual volume decrease as uterus elevates the diaphragm
- GI
- Reflux symptoms or heart burn à30 – 80% of pregnant women
§ r/t more relaxed lower esophageal sphincter
§ partly because of increased progesterone and estrogen and partly b/c of
increase in abdominal pressure as the pregnancy progresses
- decreased stomach and intestinal motility occurs allowing for greater
absorption of nutrients, can also lead to constipation
- enlarged gallbladder à contracts slower & limits ability to completely empty
§ lead to bile stasis increasing risk of gallstones à choleostasis
- Renal
- Kidneys increase in length and weight – increased volume in renal pelvis with
dilated renal calyces
- Ureters dilate, increases urine volume and predispose to UTIs
- Increased renal blood flow and GFR à small amounts of glucosuria and
proteinuria
§ Glucose and protein tested every antenatal visit
- SKIN
- Striae/stretch marks – abdomen, breast, thighs – late in 2nd trimester
- Hyperpigmentation (90% of women), more noticeable with darker complexions
§ d/thigher levels of melanocyte-stimulating hormone, estrogen and
progesterone => all have properties to to stimulate the melanocyte to
produce more melanin
- Linea nigra à hyper pigmented line on the abdomen
- Chloasma or mask of pregnancy à irregular patches on the face and/or neck

Infertility
Definition and Trends
- Failure of a couple to conceive after one year of unprotected intercourse
- If a woman is over 35, it is a 6 month period of this time
- Prevalence (2001) à 8.5% = 250,000 infertile couples
Causes
- Women ~40%
- Non-modifiable: ovulatory disorders, PID, endometriosis, congenital anomalies,
environmental and occupation exposure
§ Hormonal, PCOS à excess male hormones, recurrent miscarriages
§ PID & endometriosis à fallopian tube occlusion

REPRODUCTION 13
 - Modifiable: age, weight, exercise, stress/psychological factors,
tobacco/alcohol/ substance abuse
§ Advanced maternal age can impact fertility
§
- Men ~30 to 40%
- Non-modifiable: sexual dysfunction, semen, or sperm quality, quantity, mobility
§ Semen analysis
- Modifiable: smoking, exercise, factors, alcohol/abuse
- Couples
- Unexplained (idiopathic) ~10 to 20%
- Connection b/w immune and reproductive system
§ Women have more reactive immune system, can lead to increased
autoimmunity and development of anti-sperm antibodies
Ovulation Disorders
- Anovulation
- Caused by a breakdown in any one of the feedback pathways
- Young woman achieves menarche, can take years for HPO axis to mature and
be ready to ovulate regularly
- Regular cycle may be disrupted d/t alterations – less than 24 days or more than
36 days
- Stress, weight changes, or idiopathic
- Amenorrhea
- Ovarian hormone secretion profile & gonadotrophin levels
- Ovarian hormone secretion normal à uterine function as main cause of issue
§ Uterus present?
§ Sx?
§ Pregnancy could cause loss of menses
§ Increased OHS à enlarged ovaries or PCOS
§ Decreased OHS à gonadotropin levels; low or normal à other hormones
i.e. adrenals or steroids
• Increased prolactin – suppress pituitary gland response; can be d/t
prolactinoma or anorexia (chronic starvation)
- Alterations in thyroid gland à cause changes in cycle length and blood flow,
lead to oligomenorrhea (cycles longer than 6 days) and potential ovarian failure
§ Hypothyroidism à interfere with normal GnRH section w/c is essential for
follicular dev’t and ovulation
§ Decrease in LH à menstrual dysfunctions; gonadal dysfunctions may
decrease amount of thyroid hormone available for ovarian fx
- Thyroid found on oocytes and granulosa cells
- hCG and maternal thyroxine à required to achieve fertilization, blastocyst
development, and fetal brain development
- ovarian cysts àmay impact ovulation; send altered feedback signals to the HPO
axis that may result in irregularities in the cycle
- PCOS à extreme form of cystic ovary; results in chronic anovulation,
endometrial hyperplasia and other pathologic conditions

REPRODUCTION 14
Polycystic Ovarian Syndrome (PCOS)

- Pic on the left: string of pearls on u/s of PCOS

- Normal ovarian volume: 9 mL
- Endocrine disorder
- Associated with primarily hyperandrogenemia +/- anovulation and its associated
infertility and with the clinical manifestations of oligomenorrhea (less frequent menses),
hirsutism (excess hair growth), and acne
- Unknown exact prevalence
- Increasing obesity rates linked
- Genetic basis suspected
- Follicles in ovaries à greatly increased; overproduce androgens leading to
androgenemia
- Criteria
- Increased volume > 9mL
- 10 or more follicles of 2-18 mm (diameter)
- Increase amount and density of ovarian stroma
- Thickening of tunica

Pathophysiology of PCOS

- Associated with metabolic defect, presents as insulin resistance and hyperinsulinemia

REPRODUCTION 15
 - Gonadotropic effect of insulin on ovarian tissue is unaffected, further increases the
androgen production and premature cessation of follicular growth
- Insulin reduces serum sex hormone-binding globulin, a glycoprotein that binds
testosterone and estradiol in the circulation to make them inactive à causes more
biologically active steroid available
- Excess ovarian androgen + less SHBG = increase free testosterone and estrogen
- FSH lower, LH higher
- LH elevated, leads to androgens (DHEA-S) levels from adrenal cortex to be
secreted in up to 50% of PCOS patients
- Blunted FSH/LH feedback leads to stimulation for new follicles, but not to full
maturation or ovulation thus accounting for anovulatory cycles
- Treatment for PCOS
- Re-establish normal hormonal levels using oral birth control pill
- Infertility à Metformin – biguanide à used to decrease the ovarian
steroidogenesis
- Pregnant women with PCOS at risk for GDM, H-HTN, preterm birth and perinatal
mortality
- Later sequelae of PCOS include dyslipidemia, CV disease, DM or metabolic syndrome

Late Maternal Age

- Decline in fertility
- As women age, their oocytes or ova do as well; declines in quality, can be more
affected by exposure to alcohol, tobacco, and poor diet
- Higher spontaneous miscarriage – may impact ability to carry a fetus to term
- Increased risk of GDM and G-HTN
- Multifactorial
- Fertility begins to decline after the age of 35
- More linear decline in likelihood of getting pregnant
- Recent trends in Canada show that more women are experiencing first delivery
after the age of 30.

Tubal Disorders
- Infections – untreated infections or STIs can cause blockage of fallopian tubes, can
lead to infertility and higher risk of ectopic pregnancy
- Types
- PID
§ Chlamydia and gonorrhea – ascending STI infection, women have no
signs or symptoms
- Increased # of infections can significantly decrease chances for getting
pregnant as this can result in permanent injury to the fallopian tubes with the loss
of cilia function, fibrosis and even complete occlusion
- Sexually active women must advocate for themselves and request routine STI
screening at their annual pap smear
- Surgery
- Alleviate blockages, but doesn’t decrease chances of ectopic

REPRODUCTION 16
 - Abdominal or pelvic surgery can lead to development of adhesions that can
affect the fallopian tubes causing constriction or poor ovum motility
- Endometriosis
- Cause blockages
- Other causes
- Embryological (Mullerian defects)

Hysterosalpingography (HSG)
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- Done to evaluate patency of fallopian tubes
- Fluoroscopic examination performed in the radiology department
- Speculum inserted to vagina (similar to pap smear), dye is injected through a
small catheter which is placed into the uterine cavity
- Sx evaluation may also be done of the pelvis and uterus (hysteroscopy, diagnostic
laparoscopy, dye transit)
- Review pelvic structures and inside of uterus
- Dye is injected (methylene blue) and see if it will free spill from the tubes into the
peritoneal cavity
- Rare to find bilateral blockage, usually one tube is affected

Endometriosis
- Appearance of plaques of endometrial tissue on other structures in the body
- Plaques can form on any structure in the pelvis or peritoneal cavity i.e. bowel, bladder,
ovary, or fallopian tube
- Behave like they are under the regular monthly influence of the female hormones and
will swell and then slough in a similar manner to the uterine lining
- No egress or exit point for products of endometrial tissue; can cause significant pain
and scarring, depending on where these ectopic endometrial implants are
- Cause is largely unknown
- Some evidence to support retrograde menstruation
- Effects on fertility – unknown
- Initial dx by clinical suspicion
- More definitive is where plaques are found – plaque has settled on a nerve root or
ovary –
- Can be more painful than if sitting on a muscle mass

Uterine Anomalies
- Mullerian system (female genital tract)
- Pregnancy achieved and carried past the point of viability with an anomaly, there is a
higher risk of preterm delivery and malpresentation at the time of delivery, that is
breech or transverse lie
- Fibroid tumours may exist on or in the muscle layers of the uterus and alter the shape
of uterine cavity, can also result in preterm delivery or malpresentation

REPRODUCTION 17
Fibroids
1 - Subserosal

2 - Intramural

3 - Pendunculated

REPRODUCTION 18
Treatments for Infertility
Intrauterine Insemination
- Least invasive
- Involves instilling semen directly into the uterus

Ovarian Stimulation
- Clomiphene (ovulatory agent) – PO
- Follitropin (Gonal-F, a gonadotropin with active ingredient FSH)
- Increase number of mature ova in a given cycle to increase chances of
achieving pregnancy

IVF

- Sperm and ova are combined outside the body, permitted to develop for 3-5 days
and then the resultant zygotes are transferred into the woman’s uterus
- Ova collected through transvaginal aspiration of ovary under ultrasound guidance
- Excess zygotes may be frozen for future attempts
- Transfer of multiple zygotes – risk of multiple gestation pregnancy
- SOGC clinical guideline

Hypertensive Disorders of Pregnancy (HDP)

- Pre-existing HTN à dx prior to 20 wks gestation; systolic is greater than or equal to 140
mmHg or diastolic > or equal to 90 mmHg
- Gestational HTN à after 20 weeks gestation; diastolic greater than or equal to 90
mmHg or systolic greater than or equal to 140
- Diastolic is a better predictor of adverse pregnancy outcomes compared to
systolic
- Leading cause of maternal morbidity and mortality (15% maternal deaths)
- Severe GHTN (160/110)
- Systolic greater than equal to 160, diastolic greater than or equal to 110 mmHg
- Systolic greater than 160 increase risk of stroke
- Pre-eclampsia
- HTN and increasing proteinuria
- Pre-existing HTN have 10-20% risk

REPRODUCTION 19
 - GHTN before 34 weeks have 35% risk
- Complications of increased BP
- Maternal à increased risk for MI, stroke, HF, renal failure
- Fetus: placental complications à poor oxygen transfer, placental abruption,
fetal growth restriction, preterm birth, death
- Treatment
- Pre-existing GHTN à beta-blockers i.e. labetalol, metprolol; CCB i.e. nifedipine,
methyldopa-a (alpha-2 adrenergic agonist) or hydralazine (direct vasodilator)
- ACE inhibitors and ARBs are CONTRAINDICATED d/t teratogenic and fetotoxic
effects

Pre-eclampsia

Definition
- Progression of HTN with clinically significant proteinuria
Assessment
- dipstick of greater than or equal to 2
- greater than equal to 30mg/mmol urinary creatinine in a random urine sample
- greater than equal to 0.3 g/day in a 24-hour urine
- edema is excluded
- routine eval – dipstick urinalysis (screening test)
- if progressing to GHTN with new onset proteinuria, add examination of deep tendon
reflexes
- Test for Clonus
- Sign of CNS irritability
- Predictor of seizure activity

Risk Factors
- Advanced maternal age (> 40 y/o)
- First continuing pregnancy
- Family or personal history of preeclampsia
- Interval pregnancy less than 2 years or greater than 10 years
- Use of reproductive technology
- Multiple gestation
- Elevated BP at initial prenatal visit

REPRODUCTION 20
 - 35% of women who develop GHTN before 34 weeks will progress to
preeclampsia with high perinatal (16%) and maternal (2%) complications

Treatment
- Begin in pre-conception period
- Counselling women considering getting pregnant to adopt a healthy lifestyle
(diet, exercise, control pre-existing HTN)
- Tx depends on gestational age and disease severity
- ONLY CURE IS DELIVERY OF BABY
- Tx goals of GHTN in early phase à control BP w/ betablockers or methyldopa
- With addition of preeclampsia esp before 34 weeks gestation à corticosteroid therapy
should be given to all women (betamethasone IM x 2) to facilitate lung maturation
- After 37 weeks, the woman presents with preeclampsia à induction and
delivery

Pathophysiology
- Preeclampsia à leads to uteroplacental mismatch
- Incomplete trophoblastic invasion and placental implantation causing shallow
vessel development
- Immunological maladaptation b/w maternal/paternal tissue
- Oxidative stress d/t high # of leukocytes, inflammatory cytokines (TNF-a and IL),
prostaglandins w/ free radicals
- Mismatch à feto-placental demands are higher than maternal supply, promotes
inflammatory anti-angiogenic mediators lead to endothelial activation
- Endothelial activation occurs in intervillous space where placental villi meets
maternal blood

Hypertensive Disorders

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Terms
- Anti-ang factors à anti-angiogenic factors (e.g. s-Fil-1:PIGF ratio)
- ARDS à acute respiratory disease syndrome
- ATN à acute tubular necrosis
- DIC à disseminated intravascular coagulation
- PBLs à peripheral blood leukocytes
- PGs à eicosanoids (prostaglandins, prostacyclins, thromboxanes, leukotrienes)
- ROS à reactive oxygen species

Aspirin prophylaxis in Pre-eclampsia

Daily low dose aspirin (60-150 mg) after first trimester, reduces incidence of preeclampsia in
women at risk by at least 10%
- No increase in adverse maternal or fetal health outcomes such as PPH, maternal
blood loss, neonatal intracranial or interventricular bleeding, with the use of low dose
aspirin
- The benefits of low dose aspirin include a reduction of intrauterine growth restriction
and preterm births, as well as an average increase in birth eight ~130 grams
- Can’t r/o increased risk of placental abruption

Potential Sequelae
- Eclampsia
- Occurs in 1 to 3 out of 1,000 pre-eclamptic patients and includes all features of
preeclampsia with addition of seizure activity
- Obstetrical emergency
- Tx
§ Stop seizures & deliver baby
§ Placental abruption – shearing of placenta from the wall of the uterus,
effectively ending the fetus’ blood supply and lifeline
• Can have neurological sequalae for mom
§ Prevention of seizures
• Use magnesium sulfate, a non-specific muscle relaxant
§ Peak post-natal occurrence 3 to 6 days
- HELLP Syndrome (hemolysis, elevated liver enzymes, low platelets)
- Progression of hypertensive state of pregnancy pre-eclampsia and eclampsia
- Hemolysis – breakdown of blood cells
- Elevated liver enzymes – inflammation of liver, pain under the right ribcage
- Low platelets – disorder of clotting status, can lead to DIC
- TX
§ Effecting delivery in a safe and timely manner
§ Vaginal or CS occurs ASAP even if fetus is premature – can quickly
progeress to DIC
§ Maternal corticosteroids + blood products (i.e. platelets) if values are
under 50x10^9/L

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Disseminated Intravascular Coagulation
- Imbalance b/w coagulation or ability of the clot to make thrombi with fibrinolysis or
the ability to breakdown the fibrin closes
- Coagulation is overactivated, Thrombin generation promoted, body consumes
clotting factors leading to abnormal bleeding, even severe hemorrhage

Main initiating factor: over expression of tissue factor

1 and 2 – TF along with other proinflammatory mediators such as IL-1, IL-6 or IL-8 or adhesion
modules continue to facilitate the secretion of TF from endothelial cells of monocytes

3 – TF is responsible for activating the coagulation cascade especially with the activation of
thrombin

4 – Plasmin works in conjunction with the thrombin limiting the fibrin clot. Clot is contained to
the local area while still permitting perfusion to the other tissues surrounding the injured area
to promote healing

5 – TNF-a stimulates plasminogen activator inhibitor (PAI) thus limiting plasmin from breaking
up any fibrin clots

6 – continuing with this spiraling process any inflammation continues to activate more
monocytes by a variety of cytokines further expressing TF leading to more fibrin deposition,

10 – Microvascular clots in organs and small vessels, leading to ischemia or necrosis – further
activate inflammatory cytokines. Clots persists, organ failure can result

7 and 8 – kinin and complement systems; can lead to increased vascular permeability,
decreased BP, shock and further platelet activation

9 – overwhelming consumption of platelets and clotting factors so that the body can no
longer clot – lead to hemorrhage. Clinically this can be identified by small petechiae or large
hematomas to bleeding from every orifice
- In case of obstetrical population, risk of placental abruption or PP hemorrhage that
becomes uncontrollable is high.

Supportive needs – include frequent BP and V/S, blood work, intravenous access (2 or more
large bore catheters, oxygenation, large numbers of blood products – including packed
RBC’s, fresh frozen plasma, platelets and cryoprecipitate, fluids such as N/S, R/L. ensure mom
stays warm especially with large numbers if fluids; monitor blood loss, document as you go,
provide controlled environment for mom and family

Post-Partum Hemorrhage
1) Definition: excessive bleeding that occurs 1st 24 hours after delivery
2) Risk Factors

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 - Tone
§ Abnormal tone – atony
§ Overdistention of uterus – multiple gestation, polyhydramnios, fetal
macrosomia, bladder distention preventing uterine contraction,
prolonged labour; retained placental tissue, obstetrical lacerations or
trauma, and maternal intrinsic bleeding defects (Von Willebrand’s
disease, ITP).
§ Active management of 3rd stage – delivery of placenta
• Administration of a dose of oxytocin with the delivery of the anterior
shoulder, IM, IV, or IV bolus
- Tissue
- Trauma
- Thrombin
3) Treatment
- Resuscitation
§ hemorrhagic shock
§ assess airway, breathing, oxygen, ensure IVs
§ frequently monitor V/S, record values and interventions
§ uterine massage – promoted production of prostaglandins and lead to
uterine contractions
- Management
§ Uterotonics
§ Controlled cord traction
§ Uterine massage
- Medications
§ Uterotonics – oxytocin, ergotamine, misoprostol
- Surgery
§ Hysterectomy – last resort
4) Nursing responsibilities
- Monitor v/s at regular intervals – policies of institution
- Excessive bleeding – monitor the amount by number of pads/towels saturated,
by weight of items used to staunch the flow, or by volume should a suction
device be used

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PPH Algorithm
- Active management of 3rd stage to help prevent PPH
- Distinguish between normal bleeding and PPH
- Assess for risk factors (4Ts)
- Resuscitation (support CV function)
- Massive hemorrhage > blood products, vasopressors, surgery

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Gestational Diabetes (GDM)
Definition: altered glucose metabolism that only occurs in pregnant state

Canadian Diabetes Association guidelines

- Untreated GDM leads to increased maternal and perinatal morbidity
- Intensive tx associated with outcomes similar to those of the general population
Prevalence
- 4% non-aboriginals; between 8 and 18% in aboriginals
Risk Factors
- Previous GDM
- Previous delivery of a macrosomic infant (>4,000 gm at birth)
- Ethnicity with high risk (aboriginal, southeast Asian or African)
- Age > 35 years
- PCOS

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 - Obesity
Screening
- Antenatal visit – urine dipped for presence of glucose
- CDA – universal screening of all pregnant women between 24- and 28-weeks
gestational age with a 50 gm oral glucose challenge
- Non-fasting, drinks 50 gm of syrup-like drink, and 1 hour later the serum blood
work is drawn
- Blood glucose less than 7.8 mmol/L following a 50 g OGTT = normal
- BG between 7.8 and 11 mmol/L would require a subsequent confirmatory or dx test; if
one if the values is exceeded à pt diagnosed with GDM
- BG > or equal to 11.1 mmol/L during initial 50g glucose challenge à immediate dx of
GDM

Treatments
- Medical nutritional management
- Client education
- Frequent blood sugar monitoring by glucometer
- CDA recommends very tight glucose targets
- Lifestyle modifications and diet insufficient – add insulin
- Glyburide and metformin

Pregnancy and Blood Sugar

- Fetus receives blood glucose across placenta but not insulin
- Maternal and fetal effects
- Macrosomia à insulin acts like a growth hormone, increases birth weight
§ Shoulder dystocia during vaginal delivery, lead to permanent injury of
brachial plexus of the newborn
§ CS for suspected macrosomia
- Perinatal mortality
- Potential link to pre-eclampsia
- Neonatal complications
§ Hypoglycemia
§ Hypocalcemia
§ Hyperbilirubinemia
§ Polycythemia
- Other long-term effects of diabetes
§ Impaired glucose tolerance & obesity

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