Reproductive Health: Pap Smear, HPV, Infertility, Endometriosis, PCOS, and Fibroids

Introduction

Reproductive health encompasses cervical cancer screening, prevention of sexually transmitted infections, evaluation and management of infertility, and common gynecologic conditions including endometriosis, polycystic ovary syndrome, and uterine fibroids. These conditions affect millions of women and can significantly impact fertility, quality of life, and long-term health.

Cervical Cancer Screening (Pap Smear)

Screening Guidelines

Population	Screening Test	Frequency	Recommendation
Age <21	None	N/A	No screening
Age 21-29	Pap smear alone	Every 3 years	Accept primary HPV testing
Age 30-65	Pap + HPV (co-test) or primary HPV every 5 years or Pap alone every 3 years	Every 5 years (co-test or HPV); every 3 years (Pap alone)	Preferred: co-testing or primary HPV
Age >65	Stop after adequate screening	None	Adequate = 3 negative Paps in 10 years or 2 negative co-tests
Post-hysterectomy	Stop if cervix removed and no prior CIN2+	None	Continue if prior CIN2+ or cervix intact
HPV vaccinated	Same as unvaccinated	Same	No change in protocol

Results Interpretation

Result	Category	Risk	Management
NILM	Negative	Lowest	Routine screening
ASC-US	Atypical squamous cells of undetermined significance	Low (5-10% CIN2+)	Reflex HPV testing: if HPV+, colposcopy; if HPV-, routine screen
LSIL	Low-grade squamous intraepithelial lesion	Moderate (15-30% CIN2+)	Colposcopy (non-pregnant adults)
ASC-H	Atypical squamous cells, cannot rule out HSIL	High	Colposcopy + endocervical sampling
HSIL	High-grade squamous intraepithelial lesion	Very high (70%+ CIN2/3+)	Colposcopy + endocervical sampling; consider LEEP
AGC (atypical glandular cells)	Glandular cell abnormality	High	Colposcopy, endocervical curettage, endometrial sampling
AIS (adenocarcinoma in situ)	Glandular precancer	Very high	Cervical conization

Cervical Cancer Staging

Stage	Description	5-Year Survival
I	Confined to cervix	80-95%
II	Beyond cervix, not to pelvic wall or lower 1/3 vagina	60-80%
III	Extends to pelvic wall or lower 1/3 vagina; hydronephrosis	35-50%
IV	Beyond pelvis; bladder/rectal mucosa; distant metastases	15-20%

HPV Vaccine

Vaccines Available

Vaccine	HPV Types Covered	Protection	Dosing	Available in US
Gardasil 9	6, 11, 16, 18, 31, 33, 45, 52, 58	90% of cervical cancers, 90% of genital warts	2 or 3 doses	Yes (current standard)

Recommendations

Population	Recommendation	Dosing Schedule
Routine age	11-12 years (can start at 9)	2 doses if started before 15th birthday (0, 6-12 months)
Catch-up females	13-26 years	3 doses if started after 15th birthday (0, 2, 6 months)
Catch-up males	13-21 years (26 if high risk)	Same as above
Immunocompromised	All ages 9-26	3 doses regardless of age at initiation
Shared clinical decision	Adults 27-45	3 doses; limited benefit at this age

Vaccine Safety

Concern	Evidence
Common side effects	Pain/redness at injection site (80%), fever, fatigue, headache (10-20%)
Syncope	5-10 per 100,000 (observe 15 min after injection)
Autoimmune disease	No increased risk in large studies
Guillain-Barre syndrome	No causal link established
Complex regional pain syndrome	No increased risk in large studies
Fertility	Does NOT cause infertility; may prevent HPV-related fertility issues

Infertility

Definitions

Term	Definition
Infertility	Failure to achieve pregnancy after 12 months of regular unprotected intercourse (6 months if woman >35)
Primary infertility	No prior pregnancy
Secondary infertility	Prior pregnancy but unable to achieve another
Recurrent pregnancy loss	2+ consecutive pregnancy losses
Subfertility	Reduced fertility (prolonged time to pregnancy but may conceive without treatment)

Causes

Category	Female Factors	Male Factors
Ovulatory (25-30%)	PCOS (most common), hypothalamic amenorrhea, premature ovarian insufficiency, thyroid dysfunction	Hypogonadotropic hypogonadism (rare)
Tubal/Peritoneal (20-30%)	Tubal blockage (prior PID, ectopic, endometriosis, surgery), adhesions, hydrosalpinx	Vasal obstruction, congenital absence of vas deferens
Uterine (5-10%)	Fibroids (submucosal), polyps, Asherman syndrome, mullerian anomalies	N/A
Cervical (1-5%)	Cervical stenosis, hostile cervical mucus	Retrograde ejaculation, anti-sperm antibodies
Male factor (30-40%)	N/A	Varicocele (most common), sperm production issues, genetic (Y-microdeletion, CF), obstruction
Unexplained (15-30%)	No cause identified after standard evaluation	Same

Infertility Evaluation

Test	Female	Male
History	Menstrual history, prior pregnancies, gynecologic history, sexual history	Pubertal history, prior pregnancies, genitourinary history, sexual history
Ovulation assessment	Mid-luteal progesterone (day 21 of 28-day cycle), ovulation predictor kits, BBT charts	N/A
Ovarian reserve	Day 3 FSH, estradiol, AMH, antral follicle count (AFC)	N/A
Imaging	Pelvic ultrasound (Day 2-5), saline infusion sonography (SIS), hysterosalpingogram (HSG)	Testicular ultrasound if indicated
Hormonal	TSH, prolactin, FSH, LH, estradiol, testosterone (if PCOS concern)	FSH, LH, total and free testosterone, prolactin
Genetic	Karyotype (if recurrent loss), carrier screening	Karyotype, Y-microdeletion, CF mutation
Semen analysis	N/A	Standard: volume, concentration, motility, morphology, pH, WBCs

Semen Analysis Parameters (WHO 5th Edition)

Parameter	Lower Reference (5th percentile)
Volume	1.5 mL
Sperm concentration	15 million/mL
Total sperm number	39 million
Total motility	40% progressive or non-progressive
Progressive motility	32%
Normal morphology (strict Kruger)	4%
Vitality (live sperm)	58%
White blood cells	<1 million/mL

Treatment

Problem	Treatment Options
Ovulatory dysfunction (PCOS)	Letrozole (first-line), clomiphene citrate, metformin (adjunct), gonadotropins
Ovulatory dysfunction (hypothalamic)	Pulsatile GnRH or gonadotropins
Tubal factor	Surgical correction or IVF
Male factor (mild-moderate)	IUI; if severe, ICSI-IVF
Endometriosis-related	Surgical excision, then IUI or IVF
Unexplained	Expectant management (3-6 months), then OI + IUI, then IVF
Recurrent pregnancy loss	Karyotype, treat underlying cause, PGT-A for some
Premature ovarian insufficiency	Donor egg, donor embryo, adoption

Assisted Reproductive Technology (ART)

Procedure	Description	Typical Live Birth Rate Per Cycle
IUI (intrauterine insemination)	Washed sperm placed into uterus at ovulation	8-15% (with OI)
IVF (in vitro fertilization)	Ovarian stimulation, egg retrieval, fertilization, embryo transfer	35-50% (<35); 25-35% (35-37); 15-25% (38-40); 5-15% (>40)
ICSI (intracytoplasmic sperm injection)	Single sperm injected into egg	Performed as part of IVF for male factor
PGT (preimplantation genetic testing)	Embryo biopsy for genetic testing	Adds 1-2 weeks; transfer frozen embryo after results
FET (frozen embryo transfer)	Thawed embryo transfer	35-50% (comparable to fresh with better uterine receptivity)

Endometriosis

Pathophysiology

Aspect	Detail
Definition	Presence of endometrial-like tissue (glands and stroma) outside the uterus
Prevalence	6-10% of reproductive-age women; 30-50% of women with infertility
Locations	Ovaries (endometriomas), uterosacral ligaments, Pouch of Douglas, peritoneum, fallopian tubes, bowel, bladder
Theories	Retrograde menstruation (Sampson), coelomic metaplasia, lymphatic/vascular spread, stem cell theory
Hormonal dependence	Estrogen-dependent; symptoms wax/wane with cycle; usually regresses with menopause

Symptoms

Symptom	Prevalence	Characteristics
Dysmenorrhea (painful periods)	60-90%	Secondary dysmenorrhea (worsens over time); may start before menses and persist after
Dyspareunia (pain with sex)	40-60%	Deep pain with penetration; often worse pre-menstrually
Chronic pelvic pain	30-60%	Cyclic or non-cyclic; may be constant
Infertility	30-50%	Associated with all stages; mechanisms: adhesions, altered pelvic environment, reduced oocyte quality
Dyschezia (pain with bowel movements)	30-50%	Worse during menses
Dysuria (pain with urination)	10-30%	Cyclic bladder symptoms
Abnormal bleeding	15-20%	Heavy menstrual bleeding, pre-menstrual spotting

Diagnosis

Method	Sensitivity	Specificity	Notes
History and physical	Variable	Variable	Tender nodules on uterosacral ligaments, fixed/retroverted uterus, adnexal mass
Pelvic ultrasound	<50% for peritoneal disease; 80-90% for endometriomas	Variable	Ovarian endometriomas: “ground glass” echogenicity; no internal vascularity
MRI	70-90% (deep endometriosis)	80-95%	Best for deep endometriosis, bowel/bladder involvement
Laparoscopy (GOLD STANDARD)	90-95%	100%	Visual inspection + biopsy; staging via rASRM or Enzian classification
CA-125	Variable	Low specificity	May be elevated but not diagnostic

Treatment

Goal	Options
Pain relief (first-line)	NSAIDs, combined OCP (continuous), progestins
Pain relief (second-line)	GnRH agonists (leuprolide), GnRH antagonists (elagolix), danazol (rarely used), aromatase inhibitors
Surgical	Laparoscopic excision of endometriosis (gold standard for diagnosis and treatment); ablation (less effective for deep disease)
Fertility	Surgical excision improves spontaneous conception; IVF if needed after surgery
Analgesic adjuvants	Gabapentin, amitriptyline (for neuropathic pain component)
Hysterectomy + bilateral salpingo-oophorectomy	Definitive treatment (for severe, refractory, childbearing complete)
Complementary	Acupuncture, physical therapy, dietary (anti-inflammatory)

Polycystic Ovary Syndrome (PCOS)

Rotterdam Diagnostic Criteria (2 of 3)

Criterion	Definition
Oligo- or anovulation	Infrequent (<8/year) or absent menstruation
Clinical or biochemical hyperandrogenism	Hirsutism (Ferriman-Gallwey score >8), acne, androgenic alopecia; elevated total/free testosterone, DHEAS
Polycystic ovaries on ultrasound	>20 follicles per ovary (with 2-9 mm diameter) OR ovarian volume >10 mL (transvaginal US)

PCOS Phenotypes

Phenotype	Oligo-anovulation	Hyperandrogenism	PCOM	Severity
A (Classic/NIH)	Yes	Yes	Yes	Most severe; highest metabolic risk
B (Classic/NIH)	Yes	Yes	No	Also severe
C (Ovulatory)	No	Yes	Yes	Moderate
D (Normoandrogenic)	Yes	No	Yes	Mildest

Associated Conditions

Condition	Prevalence in PCOS	Screening
Insulin resistance / type 2 diabetes	50-70% IR; 7-10% T2DM	Fasting glucose, A1c, 2-hour OGTT (75g) at diagnosis then q1-5 years
Metabolic syndrome	30-50%	Blood pressure, lipids, waist circumference, glucose
Cardiovascular disease	Increased risk	BP, lipids; treat risk factors
Non-alcoholic fatty liver disease	30-60%	LFTs, consider ultrasound
Endometrial hyperplasia/cancer	2-6x risk	Endometrial biopsy if prolonged amenorrhea or abnormal bleeding
Obstructive sleep apnea	30-60%	Symptom screening
Depression/anxiety	40-60%	PHQ-9, GAD-7
Eating disorders	Increased	Screening

PCOS Treatment

Goal	Intervention
Cycle regulation	Combined OCP (first-line), cyclic progestin (medroxyprogesterone 10 mg x 12 days/month), LNG-IUD (for endometrial protection)
Hirsutism/acne	OCP (with anti-androgen progestin), spironolactone (50-200 mg daily), eflornithine cream (Vaniqa), laser hair removal
Anovulatory infertility	Letrozole (first-line), clomiphene citrate, metformin (adjunct), gonadotropins, ovarian drilling (laparoscopic)
Weight management	Lifestyle modification (caloric restriction 500-1000 cal/day deficit, 150+ min/week exercise)
Metformin	500-2000 mg/day (for glucose metabolism, not first-line for ovulation); also for prevention of GDM (controversial)
Insulin resistance	Lifestyle first; metformin; if T2DM develops, standard diabetes management

Uterine Fibroids (Leiomyomas)

Classification by Location

Type	Location	Symptoms
Submucosal	Beneath endometrium, protruding into uterine cavity	Heavy bleeding (most symptomatic), pain, infertility
Intramural	Within myometrium	Heavy bleeding, pressure, pain (size-dependent)
Subserosal	Beneath serosa, protruding outward	Pressure effects on bladder/rectum, pain (if large or pedunculated)
Pedunculated	Attached by stalk (submucosal or subserosal)	Torsion risk (acute pain if pedunculated subserosal)
Cervical	In cervix	Pain, bleeding, obstruction

Symptoms

Symptom	Frequency	Mechanism
Heavy menstrual bleeding (menorrhagia)	60-80%	Increased endometrial surface area, altered venous drainage, congestion
Pelvic pressure/fullness	30-50%	Mass effect on bladder, rectum, ureters
Bladder symptoms (frequency, urgency)	30-50%	Compression of bladder (anterior/subserosal fibroids)
Constipation/tenesmus	15-30%	Compression of rectum (posterior fibroids)
Dysmenorrhea	30-50%	Increased uterine contractility, congestion
Infertility	5-10%	Submucosal fibroids: alter implantation; tubal ostia compression
Acute pain	<5%	Torsion of pedunculated fibroid or red degeneration (pregnancy)

Risk Factors

Factor	Relative Risk	Notes
Age	Increases with reproductive age; peak 40-50	>40: 60-80% prevalence
Race (African American)	2-3x	Earlier onset, more numerous, larger, more symptomatic
Nulliparity	1.5-2x	Protective: term pregnancy decreases risk
Early menarche	1.2-1.5x	Longer estrogen exposure
Obesity	1.5-2x	Increased estrogen production
Hypertension	1.5x	Unknown mechanism
Red meat consumption	1.5x (diet high in red meat)	Dietary factors
Vitamin D deficiency	1.5-2x	Vitamin D inhibits fibroid growth

Treatment

Approach	Options	Best For
Expectant management	Observation with serial US	Asymptomatic, small fibroids; perimenopausal women
Medical	NSAIDs, tranexamic acid, OCPs, progestins, LNG-IUD (Mirena), GnRH agonists (leuprolide), GnRH antagonists (elagolix, relugolix), aromatase inhibitors	Symptom control; pre-operative shrinkage
Interventional	Myomectomy (hysteroscopic, laparoscopic, open), uterine artery embolization (UAE), MR-guided focused ultrasound (MRgFUS), radiofrequency ablation (Acessa, Sonata)	Symptomatic women desiring fertility (myomectomy) or wanting to avoid hysterectomy
Surgical	Hysterectomy	Definitive; for women who have completed childbearing