NSG210 Durham Ch. 3: Genetics, Conception, Fetal Development, and Reproductive Technology

Source: Durham & Chapman, Maternal-Newborn Nursing: The Critical Components of Nursing Care 4e, Chapter 3, pp. 39-55 (textbooks/DURHAM_OB_CH03.pdf, also in textbooks/exam01/). Week 03 reading; on Exam 1 (fertilization, fetal development, and teratogens are on the Exam 1 OB test map). See also nsg210-week-03b-summary.

Learning Outcomes

1. Discuss genetics in the care of the childbearing family.
2. Identify critical components of conception, embryonic development, and fetal development.
3. Describe development and function of the placenta and amniotic fluid.
4. List common causes of infertility.
5. Describe common diagnostic tests for infertility.
6. Describe common assisted fertility methods.
7. Discuss ethical and emotional implications of assisted reproductive therapies (ART).

I. Genetics

• Genes: basic units of heredity, made of DNA and protein; human genome about 30,000 genes
• 46 chromosomes per cell: 22 homologous pairs (autosomes) and one pair of sex chromosomes (XX female, XY male)
• Genotype: genetic makeup; phenotype: outward expression (eye color, height)
• Genetics: study of single genes and heredity; genomics: all genes and their interrelationships (Critical Component)
• Advances help prevent and diagnose disease, predict risk, personalize treatment

A. Inheritance patterns

• Dominant gene expressed when paired with a recessive gene; recessive trait shows only when both genes are recessive
• Autosomal recessive: disease when both genes in the pair are defective; one defective gene makes a carrier who can pass it on but is unaffected; two carrier parents - 1 in 4 affected, 2 in 4 carriers, 1 in 4 unaffected (Fig. 3-1); examples cystic fibrosis, sickle cell anemia, thalassemia, Tay-Sachs, PKU
• Autosomal dominant: disease when one or both genes carry the defect; affected parent - each child 50% chance (Fig. 3-2); examples Huntington’s disease, familial hypercholesterolemia, xeroderma pigmentosum
• X-linked: mutation only on the X chromosome; males with the mutated X are affected (no matching gene on Y, so even a recessive gene acts dominant); females with one affected X are carriers; carrier mother - sons 50% affected, daughters 50% carriers (Fig. 3-3); examples hemophilia, Duchenne muscular dystrophy
• Y-linked: mutation only on Y; passed only from father to son

Genetic diseases (Table 3-1):

• Sickle cell anemia (R): most common genetic disease in people of African ancestry; rigid hemoglobin crystals distort RBCs, less oxygen-carrying capacity
• Cystic fibrosis (R): most common in people of European ancestry; thick mucus clogs bronchi and pancreatic ducts; chronic respiratory infection, pulmonary failure
• Tay-Sachs (R): most common in people of Jewish ancestry; neuron degeneration, death by age 2
• PKU (R): cannot metabolize phenylalanine; severe intellectual and physical disability prevented by low-phenylalanine diet from birth
• Huntington’s disease (D): uncontrollable muscle contractions at 30-50, then loss of memory and personality
• Hemophilia (X-linked): lack of factor VIII impairs clotting; controlled with factor VIII
• Duchenne muscular dystrophy (X-linked): muscle replaced by fat and scar; often fatal before 20 from cardiac involvement

B. Genomic medicine

• Human Genome Project completed 2003 (13 years)
• Genomic medicine (NHGRI): using a person’s genomic information in clinical care
• Examples: newborn screening; cell-free DNA as a cancer biomarker; pharmacogenomics; drugs for genetic diseases (ivacaftor for a CF mutation)

C. Genetic testing

• Carrier testing: identifies people carrying one copy of a mutation when there is family history; testing both partners gives risk of an affected child
• Preimplantation genetic diagnosis: a cell from an IVF embryo is tested before transfer
• Prenatal testing: early detection of trisomy 21, hemophilia, Tay-Sachs
• Newborn screening: treatable disorders early in life
• Higher-risk couples: maternal age over 35; prior pregnancy with a genetic disorder or abnormality; one or both partners with a genetic disorder; family history
• Prenatal diagnosis allows gene therapy (when available), preparation, or genetic counseling about continuing or terminating

Nursing actions:

• Continuing pregnancy: more information about the disorder; support groups; reliable websites; explain grief over loss of the “dream child” is normal; encourage open communication between partners
• Terminating pregnancy: explain stages of grief; grief is normal; encourage sharing emotions; support group referral
• Explain diagnostic procedures (purpose, findings, side effects); clarify information from providers and counselors; know local genetic counseling services, access, and referral

II. Teratogens

• Teratogens: drugs, viruses, infections, or other exposures that can cause embryonic or fetal abnormalities
• Effect depends on length, amount, and timing of exposure
• Most vulnerable during organogenesis - the first 8 weeks of gestation (gross structural defects)
• After 13 weeks: growth restriction or reduced organ size
• Critical Component: toxoplasmosis (protozoan in cat feces and rare beef or lamb) can cause fetal demise, intellectual disability, blindness; avoid cleaning litter boxes and eating rare meat

Teratogenic agents (Table 3-2):

III. Reproductive Anatomy

A. Male

• Scrotum: about 96 F (35.6 C), lower than body temperature, for viable sperm production
• Testes: descend before birth; seminiferous tubules make sperm (spermatogenesis); sperm travel via rete testis to epididymis
• Epididymis: coiled tube on posterior testis where sperm mature
• Ductus (vas) deferens: from epididymis over and behind the bladder to the ejaculatory duct
• Ejaculatory ducts: receive sperm and seminal vesicle secretions, empty into urethra
• Seminal vesicles: alkaline secretions with fructose (sperm energy), increase motility
• Prostate: surrounds first inch of urethra; alkaline fluid increases motility
• Bulbourethral (Cowper’s) glands: alkaline coating neutralizes acidic urine in urethra
• Urethra and penis: erection when arteries dilate and sinuses fill

B. Female

• Ovaries: about 4 cm; held by ovarian and broad ligaments; thousands of primary follicles at birth, each with an oocyte; follicle cells secrete estrogen; mature follicle is the graafian follicle
• Fallopian tubes (oviducts): fertilization occurs here; fimbriae sweep ovum in; peristalsis moves it to the uterus
• Uterus: upside-down pear, about 3 x 2 x 1 inches; fundus (top), body, cervix (opens to vagina); endometrium has a permanent basilar layer and a functional layer that thickens monthly and sheds if no implantation
• Vagina: about 4 inches; receives sperm, menstrual outflow, birth canal in second stage
• Vulva: clitoris (erectile tissue), labia majora and minora (protect openings), Bartholin’s glands (lubricate)

IV. Menstrual Cycle (Fig. 3-8)

Ovarian cycle:

1. Follicular phase: day 1 of menses, 12-14 days; graafian follicle matures under LH and FSH; follicle produces estrogen
2. Ovulatory phase: begins with estrogen peak, ends with release of the oocyte (ovulation); LH surges 12-36 hours before ovulation; just before the surge estrogen falls and progesterone rises
3. Luteal phase: about 14 days after ovulation; empty follicle becomes the corpus luteum, producing high progesterone and low estrogen; if pregnancy, corpus luteum keeps secreting until the placenta takes over; if not, it degenerates, progesterone falls, menses begins

Endometrial cycle:

1. Proliferative phase: after menses until ovulation; endometrium thickens and becomes more vascular (estrogen)
2. Secretory phase: after ovulation until menses; continued thickening (progesterone from corpus luteum); secretes glycogen for the blastocyst if pregnancy occurs
3. Menstrual phase: sloughing of endometrium

V. Gametogenesis

• Mitosis: one cell divides into two identical diploid daughter cells (46 chromosomes)
• Meiosis: two successive divisions producing haploid cells (23 chromosomes)
• Oogenesis: FSH stimulates follicle growth and estrogen; estrogen matures the ovum; oogonium divides by mitosis into primary oocyte and new stem cell; meiosis produces one mature ovum plus polar bodies - one functional ovum per primary oocyte
• Spermatogenesis: FSH stimulates sperm production; LH stimulates testosterone; testosterone matures sperm; meiosis of each primary spermatocyte produces four spermatids (four functional sperm); mature spermatids are spermatozoa

VI. Conception and Implantation

• Conception (fertilization): sperm nucleus enters oocyte nucleus, normally in the outer third of the fallopian tube; fertilized oocyte is the zygote (46 chromosomes)
• Requirements: ovulation and ovum in the tube; sperm deposited and reaching the tube; one sperm penetrates the ovum
• Cleavage: mitotic division of the zygote
• Day 3: morula (16-cell solid sphere)
• About day 5: enters uterus as a blastocyst - inner cell mass (embryoblast, becomes embryo) and outer cell mass (trophoblast, aids implantation and becomes part of placenta)
• Implantation: begins about day 5-6; progesterone thickens and vascularizes endometrium; trophoblast (now chorion) enzymes digest endometrial surface; usually upper posterior uterine wall
• Twins: monozygotic (identical) - one fertilized ovum splits; dizygotic (fraternal) - two ova fertilized by two sperm

VII. Embryonic and Fetal Development

A. Embryo (implantation through 8 weeks)

• Organogenesis occurs during this period
• Primary germ layers begin about day 14 (Table 3-3):
  • Ectoderm (outer): epidermis, hair, nails, sweat glands; nervous system; pituitary; adrenal medulla; lens and cornea; inner ear; oral and nasal mucosa; salivary glands
  • Mesoderm (middle): dermis; bone and cartilage; skeletal, cardiac, most smooth muscle; kidneys; adrenal cortex; bone marrow and blood; lymphatic tissue; blood vessel lining
  • Endoderm (inner): mucosa of esophagus, stomach, intestines; respiratory epithelium including lungs; liver and gallbladder mucosa; thyroid; pancreas
• Heart forms in week 3, begins beating and circulating blood in week 4
• By end of week 8: clearly human, about 3 cm, all organ systems formed

B. Fetus (week 9 to birth) (Table 3-4, crown-rump length)

C. Fetal circulation (Fig. 3-13)

• Umbilical vein brings highly oxygenated blood from the placenta
• Ductus venosus: connects umbilical vein to inferior vena cava, sending most oxygenated blood to the right atrium
• Foramen ovale: opening between right and left atria; shunts oxygenated blood to the left atrium; closes after birth as more blood returns to the left atrium (full closure up to 3 months)
• Ductus arteriosus: connects pulmonary artery to descending aorta; diverts most blood away from the lungs; constricts after birth in response to higher oxygen and prostaglandin changes

VIII. Placenta, Membranes, Amniotic Fluid, Cord

A. Placenta (Fig. 3-14)

• Formed from fetal and maternal tissue
• Fetal side: chorionic membrane (from trophoblast) and chorionic villi, which embed in the decidua basalis and form fetal vessels
• Decidua (endometrium in pregnancy): basalis (under the blastocyst, forms maternal placenta), capsularis, vera
• Maternal side divided into lobes called cotyledons
• Placental membrane keeps maternal and fetal blood separate but allows exchange of gases, nutrients, electrolytes
• Functions:
  • Metabolic and gas exchange: fetal CO2 and wastes diffuse to maternal blood; glucose, amino acids, O2 move to fetus by diffusion and active transport
  • Hormones: progesterone (supports implantation, decreases uterine contractility); estrogen (enlarges breasts and uterus); hCG (maintains the corpus luteum until the placenta takes over; measured in pregnancy tests; rises rapidly in first trimester then declines); hPL, also called human chorionic somatomammotropin (regulates glucose for fetal growth, prepares breasts for lactation)
• Rubella, CMV, and drugs cross the placenta; avoid FDA category C, D, X drugs; consult provider before any medication or vaccine (Critical Component)
• Fully functional by weeks 8-10; at term 15-25 cm diameter, 3 cm thick, about 600 g

B. Membranes and amniotic fluid

• Amniotic sac (“bag of waters”): inner amnion (from embryoblast) and outer chorion (from trophoblast); barrier against bacteria from vagina
• Amniotic fluid: clear, mostly water, with proteins, carbohydrates, lipids, electrolytes, fetal cells, lanugo, vernix
• Produced by amnion in first trimester, by fetal kidneys in second and third trimesters
• Volume peaks at 800-1,000 mL around 34 weeks; 500-600 mL at term
• Functions: cushions from maternal movement; prevents adhesion to membranes; allows movement for symmetric musculoskeletal development; consistent temperature
• Polyhydramnios (hydramnios): excess, 1,500-2,000 mL; associated with chromosomal, GI, cardiac, neural tube disorders
• Oligohydramnios: under 500 mL at term or 50% reduction; usually decreased placental function; associated with congenital renal problems

C. Umbilical cord

• Two umbilical arteries (deoxygenated blood) and one umbilical vein (oxygenated blood)
• Wharton’s jelly protects vessels from compression
• Usually inserts centrally; about 55 cm long
• Critical Component: count cord vessels after birth; a two-vessel cord (one artery, one vein) carries about 20% chance of cardiac or vascular defect - document and report

IX. Infertility

• Inability to conceive after 12 months of unprotected intercourse (6 months if woman over 35)
• Prevalence: 12.6% of women 15-29; 22.1% at 30-39; 26.8% at 40-49
• Cause identified in about 80%; male factor in 35% (alone in 8%)

A. Male causes

1. Endocrine: pituitary or hypothalamic disease, low LH, FSH, testosterone
2. Spermatogenesis (gonadotoxins): chemotherapy, calcium channel blockers, heroin, alcohol; prostatitis, STIs, mumps after puberty; systemic illness; heat to testes (hot tubs, tight underwear, cycling); pesticides; pelvic radiation
3. Sperm antibodies: after vasectomy reversal or testicular trauma; reduced motility
4. Sperm transport: vasectomy, prostatectomy, inguinal hernia, congenital absence of vas deferens
5. Disorders of intercourse: erectile dysfunction, retrograde ejaculation, hypospadias, psychosocial factors

B. Female causes

1. Ovulatory dysfunction (high treatment success): hormonal imbalance, hyper- or hypothyroidism, high prolactin, premature ovarian failure (menopause before 40), polycystic ovarian syndrome
2. Tubal and pelvic: tubal damage from PID or endometriosis; uterine fibroids narrowing the cavity and causing miscarriage
3. Cervical mucus: infection, cervical surgery (cryotherapy for dysplasia)

Risk factors (Critical Component):

• Women: autoimmune disorders, diabetes, eating disorders or poor nutrition, heavy alcohol, excessive exercise, prior gonadotoxic chemotherapy or pelvic radiation, obesity, older age, STIs
• Men: environmental pollutants, heavy alcohol, marijuana, cocaine, impotence, older age, STIs, smoking

C. Diagnosis

• Evaluate both partners (gynecologist or reproductive endocrinologist; urologist)
• STI screening
• Hormone levels: TSH, FSH, LH, anti-Mullerian hormone (AMH), testosterone
• Semen analysis: abstain 2-3 days; masturbated sample delivered within 1 hour; volume, concentration, motility, morphology, WBCs, antibody tests; may need repeats (production fluctuates)
• LH surge detection: LH rises 36 hours before ovulation; home urine ovulation predictor helps time intercourse
• Ovarian reserve testing: day 3 FSH, estradiol, AMH plus transvaginal ultrasound for ovarian volume and antral follicle count
• Sonohysterogram or hysteroscopy: evaluate uterus
• Hysterosalpingogram: dye injected through cervix under fluoroscopy; shows tubal adhesions or occlusion and uterine abnormalities (fibroids, bicornuate uterus, fistulas)

D. Treatment

Male:

• Hormonal therapy; lifestyle (stress reduction, nutrition, quit smoking, stop harmful drugs); corticosteroids for sperm antibodies; antibiotics for GU infection; repair varicocele or hernia; transurethral resection of ejaculatory ducts

Female:

• Anovulation: lifestyle changes; ovulation-stimulating drugs (clomiphene citrate - very high success; letrozole; injectable gonadotropins; GnRH pump; bromocriptine)
• Surgery to open fallopian tubes; myomectomy for fibroids; antibiotics for cervical infection

Clomiphene citrate (Clomid):

• Indication: anovulatory infertility
• Action: stimulates release of FSH and LH, causing ovulation
• Side effects: hot flashes, breast discomfort, headaches, insomnia, bloating, blurred vision, nausea, vaginal dryness
• Dose: PO 50-200 mg/day on cycle days 3-7
• Nursing: teach use and side effects; do not drive with blurred vision

E. Assisted fertility technologies (Table 3-5)

F. Emotional implications

• “Roller coaster” of hope each month and sadness with each period
• Stress, anxiety, depression in both partners; guilt; marital strain and blame; sexual dysfunction from prescribed sex; avoidance of family events with children, social isolation; lack of support if not disclosed; low self-esteem (“less of a man/woman,” “defective” body)
• Counseling ideally before treatment: effects on couple and family, treatment options, ethical dilemmas, when to stop treatment, adoption, gestational surrogacy
• Olshansky’s theory “identity as infertile”: consumed by infertility, neglect of relationships and career, isolation; difficulty perceiving self as pregnant once pregnancy occurs - previously infertile mothers vulnerable to depression
• Critical Component: infertility affects individual and couple emotional well-being; awareness improves nursing care

G. Ethical implications of ART

• ART: surgical removal of oocytes and combination with sperm in a lab (IVF, ZIFT, GIFT, ET)
• Main dilemma: surplus embryos from ovarian hyperstimulation (frozen or allowed to perish) - when does life begin, rights of the embryo
• Who owns the embryos; who decides their fate
• Access (high cost, often not insured)
• When should providers recommend stopping
• Whether and when to tell a child about donor sperm or surrogacy
• Rights and responsibilities of sperm donors and gestational surrogates
• Gestational surrogate options: surrogate inseminated with partner’s sperm, or couple’s embryo placed in surrogate’s uterus

High-Yield Numbers

• 46 chromosomes (23 pairs); genome about 30,000 genes
• Autosomal recessive: 25% affected with two carrier parents; autosomal dominant: 50%; X-linked carrier mother: 50% of sons affected
• Organogenesis: first 8 weeks; after 13 weeks teratogens mainly affect growth
• Fertilization in outer third of fallopian tube; morula day 3; blastocyst and implantation day 5-6
• Germ layers form about day 14; heart beats week 4; embryo 3 cm at 8 weeks
• FHT by Doppler at 12 weeks; surfactant begins at 24 weeks
• LH surge 12-36 hours before ovulation (36 hours for ovulation predictor tests)
• Follicular phase 12-14 days; luteal phase 14 days
• Placenta functional at 8-10 weeks; term 15-25 cm, 3 cm thick, 600 g
• Amniotic fluid peak 800-1,000 mL at 34 weeks; term 500-600 mL; polyhydramnios 1,500-2,000 mL; oligohydramnios under 500 mL
• Cord: 2 arteries, 1 vein, about 55 cm; 2-vessel cord 20% cardiac/vascular defect risk
• Scrotum about 96 F
• Infertility: 12 months (6 months if over 35); male factor 35%
• Clomiphene 50-200 mg days 3-7
• Semen analysis: abstain 2-3 days, deliver within 1 hour

Priority Nursing Actions

• Teach avoidance of teratogens, especially in the first 8 weeks: no alcohol, avoid cat litter and rare meat, review all medications and vaccines with provider
• Ask about ACE inhibitors, warfarin, carbamazepine in women planning pregnancy
• Count umbilical cord vessels at birth and report a two-vessel cord
• Support couples facing genetic diagnoses; normalize grief; refer to counseling and support groups
• Support infertile couples emotionally; screen for depression, including after achieving pregnancy
• Teach clomiphene side effects and not to drive with blurred vision

Related

• nsg210-exam-2-outline-durham-ch04 - Durham Ch. 4 physiologic changes of pregnancy
• nsg210-durham-ch05-psychosocial-cultural-pregnancy
• nsg210-week-03b-summary
• INDEX