Infertility in Reproductive Medicine

Lecture Notes for Medical Students and Residents in Obstetrics and Gynecology

Infertility in Reproductive Medicine

Updated 22 Aug 2025

Learning Objectives

By the end of this chapter, students will be able to:

  • Define infertility and understand its epidemiology

  • Identify the major causes of male and female infertility

  • Perform appropriate history taking and physical examination

  • Order and interpret relevant diagnostic tests

  • Develop evidence-based treatment plans

  • Counsel patients appropriately regarding prognosis and treatment options.

  • Recognize when to refer to reproductive endocrinology specialists

I.           Overview

Key Definitions

Fertility: The actual reproductive performance of an individual or couple, measured by the occurrence of live births. It represents the realized reproductive potential and is influenced by both biological capacity and behavioral factors.

Fecundity: The biological capacity to reproduce, encompassing the physiological ability to conceive and carry a pregnancy to term. This represents the maximum reproductive potential of an individual or couple under optimal conditions, independent of their desire to reproduce.

Fecundability: The probability of achieving pregnancy in a single menstrual cycle among couples who are trying to conceive. It is typically expressed as a monthly probability and varies with age, underlying fertility status, and timing of intercourse. Normal fecundability is approximately 20-25% per cycle in healthy couples under age 30.

Infertility: The inability to achieve pregnancy after 12 months or more of regular unprotected sexual intercourse in women under 35 years of age, or after 6 months in women 35 years and older. This definition assumes:

  • Regular sexual intercourse (2-3 times per week)

  • No use of contraception

  • Adequate exposure time for conception

Primary Infertility: Refers to couples who have never conceived despite meeting the above criteria for infertility.

Secondary Infertility: Refers to couples who have previously achieved at least one pregnancy (regardless of outcome) but are currently unable to conceive despite meeting infertility criteria.

Subfertility: A term sometimes used to describe reduced fertility that may still result in conception given sufficient time, as opposed to complete infertility. However, this term is not universally accepted and many prefer the broader term "infertility."

Sterility: The complete inability to reproduce, representing absolute infertility. This is a permanent condition that cannot be overcome with treatment (e.g., bilateral tubal occlusion, azoospermia due to genetic causes).

Epidemiology

  • Affects approximately 15% of reproductive-aged couples globally

  • Incidence increases with maternal age, particularly after age 35

  • Male factors contribute to approximately 40% of cases

  • Female factors contribute to approximately 40% of cases

  • Combined male and female factors: 10%

  • Unexplained infertility: 10%

Risk Factors

General Risk Factors:

  • Advanced maternal age (>35 years)

  • Advanced paternal age (>40 years)

  • Smoking (both partners)

  • Excessive alcohol consumption

  • Obesity or significant underweight

  • Exposure to environmental toxins

  • Chronic medical conditions

  • Previous pelvic inflammatory disease

  • History of sexually transmitted infections

II.      Female Infertility

Presentation

Patients typically present with inability to conceive despite regular unprotected intercourse. Associated symptoms may include:

  • Irregular or absent menstrual cycles

  • Painful menstruation (dysmenorrhea)

  • Pelvic pain

  • Abnormal vaginal discharge

  • Signs of hyperandrogenism (hirsutism, acne, male-pattern baldness)

  • Galactorrhea

  • Hot flashes or other menopausal symptoms

History Taking

Menstrual History:

  • Age at menarche

  • Cycle length and regularity

  • Duration and character of menstrual flow

  • Presence of dysmenorrhea

  • Date of last menstrual period

Reproductive History:

  • Duration of infertility

  • Previous pregnancies (outcomes, complications)

  • Previous contraceptive use

  • Frequency and timing of intercourse

  • Use of lubricants

Medical History:

  • Chronic medical conditions (diabetes, thyroid disorders, autoimmune diseases)

  • Previous surgeries (particularly pelvic/abdominal)

  • Medications and supplements

  • History of pelvic inflammatory disease or STIs

  • Cancer treatment history

Social History:

  • Smoking and alcohol use

  • Exercise habits and BMI

  • Occupational exposures

  • Stress levels

  • Diet and nutrition

Family History:

  • Family history of infertility

  • Genetic disorders

  • Early menopause

  • Reproductive cancers

Physical Examination

General Examination:

  • Height, weight, BMI calculation

  • Blood pressure and vital signs

  • Assessment for signs of hyperandrogenism or thyroid disease

  • Galactorrhea assessment

Pelvic Examination:

  • External genitalia inspection

  • Speculum examination (cervical visualization, discharge assessment)

  • Bimanual examination (uterine size, position, mobility; adnexal masses or tenderness)

  • Rectovaginal examination if indicated

Workup for Female Infertility

Initial Laboratory Tests:

  • Complete blood count

  • Comprehensive metabolic panel

  • Thyroid stimulating hormone (TSH)

  • Prolactin

  • Anti-Müllerian hormone (AMH)

Hormonal Assessment:

  • Day 3 FSH and LH (if regular cycles)

  • Day 3 estradiol

  • Mid-luteal progesterone (day 21 of 28-day cycle)

  • Testosterone and DHEA-S (if signs of hyperandrogenism)

  • 17-hydroxyprogesterone (if PCOS suspected)

  • Fasting glucose and insulin (if PCOS suspected)

Ovulation Assessment:

  • Basal body temperature charting

  • Ovulation predictor kits

  • Mid-luteal progesterone level

  • Transvaginal ultrasound for follicular monitoring

Anatomical Assessment:

  • Transvaginal ultrasound (baseline and throughout cycle)

  • Saline infusion sonohysterography (SIS) or hysterosalpingography (HSG)

  • Magnetic resonance imaging (if indicated)

  • Laparoscopy and hysteroscopy (if indicated)

Additional Tests (as indicated):

  • Antiphospholipid antibodies

  • Antithyroid antibodies

  • Genetic testing (karyotype, fragile X premutation)

  • Cervical cultures for gonorrhea and chlamydia

Major Causes of Female Infertility

Ovulatory Disorders (25-30%):

  • Polycystic ovary syndrome (PCOS)

  • Hypothalamic dysfunction

  • Premature ovarian insufficiency

  • Hyperprolactinemia

  • Thyroid disorders

Tubal and Peritoneal Factors (30-35%):

  • Pelvic inflammatory disease sequelae

  • Endometriosis

  • Previous ectopic pregnancy

  • Pelvic adhesions

  • Tubal occlusion or damage

Uterine and Cervical Factors (10-15%):

  • Uterine fibroids

  • Endometrial polyps

  • Intrauterine adhesions (Asherman's syndrome)

  • Congenital uterine anomalies

  • Cervical stenosis or mucus abnormalities

Age-Related Factors:

  • Diminished ovarian reserve

  • Increased aneuploidy risk

  • Decreased egg quality

III. Male Infertility

Presentation

Male partners may present with:

  • History of infertility in relationship

  • Decreased libido or erectile dysfunction

  • Ejaculatory problems

  • Testicular pain or swelling

  • History of infections or trauma

History Taking

Reproductive History:

  • Duration of infertility

  • Previous pregnancies with current or other partners

  • Sexual history (frequency, timing, dysfunction)

  • Previous fertility testing

Medical History:

  • Undescended testes (cryptorchidism)

  • Testicular trauma or torsion

  • Infections (mumps orchitis, STIs)

  • Varicocele

  • Previous surgeries (hernia repair, urological procedures)

  • Cancer treatment (chemotherapy, radiation)

  • Chronic medical conditions

  • Medications (particularly those affecting fertility)

Social and Environmental History:

  • Smoking and alcohol use

  • Drug use (particularly anabolic steroids)

  • Occupational exposures (heat, chemicals, radiation)

  • Hot tub or sauna use

  • Bicycle riding (excessive)

  • Tight clothing

Family History:

  • Genetic disorders

  • Cystic fibrosis

  • Infertility in male relatives

Physical Examination

General Examination:

  • Height, weight, BMI

  • Secondary sexual characteristics

  • Gynecomastia

  • Body hair distribution

Genital Examination:

  • Penis inspection (hypospadias, epispadias)

  • Testicular examination (size, consistency, masses)

  • Epididymal examination

  • Vas deferens palpation

  • Varicocele assessment (standing and supine)

  • Inguinal examination for hernias

Workup for Male Infertility

Semen Analysis (Primary Test):

  • Volume: Normal >1.5 mL

  • Concentration: Normal >15 million/mL

  • Total count: Normal >39 million per ejaculate

  • Motility: Normal >40% motile

  • Progressive motility: Normal >32%

  • Morphology: Normal >4% normal forms

  • pH: Normal 7.2-8.0

  • White blood cells: <1 million/mL

Additional Laboratory Tests:

  • Hormonal evaluation (if semen analysis abnormal):

    • FSH, LH

    • Total testosterone (morning level)

    • Prolactin

  • Genetic testing (if severe oligospermia or azoospermia):

    • Karyotype

    • Y chromosome microdeletion analysis

    • Cystic fibrosis mutation analysis

Specialized Testing (as indicated):

  • Post-ejaculatory urine analysis (if low volume ejaculate)

  • Testicular biopsy (if azoospermia)

  • Transrectal ultrasound

  • Antisperm antibody testing

  • Sperm DNA fragmentation testing

Testicular Biopsy: Indications and Results

Indications for Testicular Biopsy:

  • Azoospermia with normal FSH levels (suggesting obstructive azoospermia)

  • Azoospermia with elevated FSH when considering sperm retrieval for ICSI

  • Differentiation between obstructive and non-obstructive azoospermia

  • Evaluation for testicular malignancy (rare indication in infertility workup)

Biopsy Techniques:

  • Open testicular biopsy: Traditional approach with direct visualization

  • Testicular sperm extraction (TESE): Simultaneous diagnostic and therapeutic procedure

  • Microdissection TESE (micro-TESE): Enhanced technique using operating microscope

Possible Histological Results:

Normal Spermatogenesis:

  • Complete spermatogenesis present in all tubules

  • All cell types from spermatogonia to mature spermatozoa

  • Suggests obstructive azoospermia

  • Excellent prognosis for sperm retrieval

Hypospermatogenesis:

  • Reduced numbers of germ cells at all stages

  • Spermatogenesis present but decreased

  • Some mature sperm may be found

  • Moderate prognosis for sperm retrieval (60-70% success rate)

Maturation Arrest:

  • Early maturation arrest: Arrest at spermatogonial or primary spermatocyte stage

  • Late maturation arrest: Arrest at secondary spermatocyte or round spermatid stage

  • No mature spermatozoa present

  • Poor to moderate prognosis depending on stage of arrest

  • Success rate: 20-30% for early arrest, 50-60% for late arrest

Sertoli Cell-Only Syndrome (SCOS):

  • Complete absence of germ cells

  • Only Sertoli cells present in seminiferous tubules

  • Two types:

    • Complete SCOS: No germ cells in any tubule (very poor prognosis)

    • Focal SCOS: Patchy distribution with some normal tubules (better prognosis)

  • Overall sperm retrieval success rate: 10-30%

Tubular Sclerosis:

  • Seminiferous tubules replaced by fibrous tissue

  • No cellular elements present

  • Usually associated with severe testicular damage

  • No possibility of sperm retrieval

  • Worst prognosis

Peritubular Fibrosis:

  • Thickening of the tubular basement membrane

  • May be associated with reduced spermatogenesis

  • Variable prognosis depending on degree of spermatogenic preservation

Clinical Correlation of Biopsy Results:

  • Results guide treatment decisions for assisted reproduction

  • Help determine success rates for surgical sperm retrieval

  • Assist in counseling couples about prognosis

  • May identify candidates for donor sperm consideration

Major Causes of Male Infertility

Pre-testicular Causes (2-5%):

  • Hypogonadotropic hypogonadism

  • Hyperprolactinemia

  • Thyroid disorders

  • Genetic disorders (Kallmann syndrome)

Testicular Causes (65-80%):

  • Idiopathic (most common)

  • Varicocele

  • Genetic disorders (Klinefelter syndrome)

  • Infections (mumps orchitis)

  • Trauma

  • Torsion

  • Cryptorchidism

  • Cancer treatment effects

Post-testicular Causes (10-20%):

  • Obstructive azoospermia

  • Ejaculatory dysfunction

  • Congenital absence of vas deferens

  • Infections causing ductal obstruction

IV.  Treatment Approaches

Female Infertility Treatment

Ovulation Induction:

  • Clomiphene citrate: 50-150 mg days 3-7 of cycle

  • Letrozole: 2.5-7.5 mg days 3-7 of cycle

  • Gonadotropins (FSH/LH): individualized dosing with monitoring

  • Metformin: 1500-2000 mg daily for PCOS patients

Surgical Interventions:

  • Laparoscopic ovarian drilling for PCOS

  • Tubal reconstructive surgery

  • Hysteroscopic procedures (polyp/fibroid removal, adhesiolysis)

  • Endometriosis treatment

Assisted Reproductive Technologies:

  • Intrauterine insemination (IUI)

  • In vitro fertilization (IVF)

  • Intracytoplasmic sperm injection (ICSI)

  • Preimplantation genetic testing

  • Donor gametes

  • Gestational surrogacy

In Vitro Fertilization (IVF): Step-by-Step Procedure

Pre-Treatment Phase (Weeks 1-4 before cycle start)

Initial Consultation and Consent:

  • Comprehensive medical history and physical examination

  • Review of all previous testing and treatments

  • Discussion of success rates, risks, and alternatives

  • Informed consent for all procedures

  • Financial counseling and insurance verification

Baseline Testing:

  • Updated laboratory tests (within 1 year):

    • Complete blood count, comprehensive metabolic panel

    • Hepatitis B and C, HIV, RPR for both partners

    • Blood type and Rh factor

    • Rubella immunity status

  • Baseline transvaginal ultrasound

  • Mock embryo transfer (optional but recommended)

  • Semen analysis confirmation

Protocol Selection: Common stimulation protocols:

  • Long GnRH agonist protocol: Most traditional, good for normal responders

  • GnRH antagonist protocol: Shorter duration, reduced OHSS risk

  • Minimal stimulation protocol: Lower medication doses, fewer eggs retrieved

Cycle Preparation Phase (Days 1-21 of preceding cycle)

Suppression Phase (Long Protocol Only):

  • Start GnRH agonist (leuprolide 1 mg daily or nafarelin 200 μg BID) on day 21 of preceding cycle

  • Continue for 10-14 days until suppression confirmed

  • Baseline ultrasound and estradiol level to confirm suppression

  • Criteria for suppression: Estradiol <50 pg/mL, no ovarian cysts >10 mm, endometrial thickness <5 mm

Ovarian Stimulation Phase (Days 1-10 of treatment cycle)

Day 1-2: Cycle Start

  • Confirm menstrual cycle start

  • Baseline transvaginal ultrasound

  • Baseline blood work: Estradiol, LH, FSH

  • Begin gonadotropin injections

Gonadotropin Therapy:

  • Starting dose: Individualized based on:

    • Age (typically 150-300 IU daily)

    • BMI

    • Antral follicle count

    • AMH levels

    • Previous response

  • Common medications:

    • Recombinant FSH (Gonal-F, Follistim): 150-450 IU daily

    • Human menopausal gonadotropin (Menopur): 75-450 IU daily

    • Combination protocols often used

Day 3-5: First Monitoring Visit

  • Transvaginal ultrasound: Measure follicles, assess response

  • Blood work: Estradiol level

  • Adjust gonadotropin dose based on response

GnRH Antagonist Addition (Antagonist Protocol):

  • Start when lead follicle reaches 12-14 mm or on stimulation day 5-6

  • Ganirelix 0.25 mg or Cetrotide 0.25 mg daily subcutaneous

  • Continue until trigger day

Days 6-10: Intensive Monitoring Phase

  • Every 1-2 days monitoring:

    • Transvaginal ultrasound

    • Estradiol, LH, progesterone levels

    • Dose adjustments as needed

Criteria for Cycle Continuation:

  • Adequate follicular response (at least 3 follicles ≥15 mm)

  • Appropriate estradiol rise (typically doubles every 2 days)

  • No premature LH surge

  • Endometrial thickness ≥7 mm

Trigger and Egg Retrieval Phase (Days 10-12)

Trigger Criteria:

  • At least 2-3 follicles ≥18 mm diameter

  • Estradiol level appropriate for number of mature follicles

  • No premature luteinization (LH surge)

Trigger Options:

  • Standard hCG trigger: 10,000 IU Pregnyl or 250 μg Ovidrel

  • GnRH agonist trigger: 2 mg leuprolide (for high OHSS risk patients)

  • Dual trigger: Combination of both (for poor responders)

Timing: Trigger administered exactly 35-36 hours before planned retrieval

Pre-Retrieval Instructions:

  • Nothing by mouth (NPO) after midnight before retrieval

  • Arrive 1-2 hours before procedure

  • Remove jewelry, contact lenses

  • Empty bladder immediately before procedure

Egg Retrieval Procedure:

  • Anesthesia: Conscious sedation (propofol + fentanyl) or general anesthesia

  • Technique: Transvaginal ultrasound-guided follicle aspiration

  • Procedure steps:

    1. Patient positioned in lithotomy position

    2. Vaginal cleansing with sterile saline

    3. Transvaginal probe with needle guide inserted

    4. 17-gauge needle advanced through vaginal fornix into follicles

    5. Follicular fluid aspirated using gentle suction (80-120 mmHg)

    6. Each follicle aspirated completely

    7. Follicles flushed if no oocyte initially retrieved

  • Duration: 15-30 minutes depending on number of follicles

  • Recovery: 1-2 hours post-procedure monitoring

Post-Retrieval Care:

  • Monitor vital signs and pain levels

  • Assess for complications (bleeding, infection)

  • Discharge when stable (usually 1-2 hours)

  • Instructions for activity restrictions and medication compliance

Fertilization and Embryo Culture Phase (Days 0-6 post-retrieval)

Day 0: Fertilization Day

  • Oocyte assessment: Grade maturity (M1, M2, GV, degenerate)

  • Sperm preparation: Density gradient centrifugation or swim-up

  • Fertilization methods:

    • Conventional IVF: Oocytes incubated with prepared sperm (50,000-100,000 motile sperm per oocyte)

    • ICSI: Single sperm injected into each mature oocyte

  • Culture conditions: 37°C, 5-6% CO2, controlled humidity

Day 1: Fertilization Assessment

  • Check for normal fertilization 16-20 hours post-insemination

  • Normal fertilization: 2 pronuclei and 2 polar bodies

  • Abnormal fertilization: 0, 1, or >2 pronuclei

  • Document fertilization rate (typically 70-80% for IVF, 75-85% for ICSI)

Days 2-3: Cleavage Stage

  • Day 2: Expect 2-4 cell embryos

  • Day 3: Expect 6-8 cell embryos

  • Grading criteria:

    • Cell number and size uniformity

    • Degree of fragmentation

    • Presence of multinucleated cells

  • Common grading system: Grade 1 (excellent) to Grade 4 (poor)

Days 4-6: Blastocyst Development

  • Day 4: Morula stage (cell compaction)

  • Day 5-6: Blastocyst formation

  • Blastocyst grading:

    • Expansion stage (1-6)

    • Inner cell mass quality (A, B, C)

    • Trophectoderm quality (A, B, C)

  • Example: 4AA = fully expanded blastocyst with excellent ICM and TE

Embryo Transfer Phase (Day 3 or 5)

Transfer Day Selection:

  • Day 3 transfer: When limited number of embryos or poor culture conditions

  • Day 5-6 transfer: Preferred when multiple good quality embryos available

  • Single embryo transfer (SET): Preferred to reduce multiple pregnancy risk

  • Multiple embryo transfer: Consider for older patients or repeated failures

Pre-Transfer Preparation:

  • Patient preparation:

    • Full bladder for ultrasound guidance (drink 32-48 oz water 1 hour before)

    • Comfortable clothing, arrive 30 minutes early

    • Optional pre-medication: ibuprofen, antibiotics, progesterone

  • Embryo preparation:

    • Embryologist selects best quality embryos

    • Load embryos into transfer catheter

    • Confirm embryo identity with patient

Transfer Procedure:

  1. Patient positioning: Lithotomy position, similar to pelvic exam

  2. Speculum insertion: Visualize cervix, clean with sterile solution

  3. Catheter insertion:

    • Use soft, flexible catheter (Cook, Wallace, Sure-View)

    • Insert through cervical os under ultrasound guidance

    • Advance to appropriate depth (usually 4-6 cm from external os)

  4. Embryo deposit:

    • Inject embryos slowly (over 10-20 seconds)

    • Withdraw catheter slowly

    • Check catheter for retained embryos

  5. Post-transfer observation: Rest 10-30 minutes (though studies show no benefit)

Post-Transfer Instructions:

  • Resume normal activities immediately

  • Continue progesterone supplementation

  • Avoid heavy lifting or strenuous exercise for 2-3 days

  • Report severe abdominal pain, heavy bleeding, or fever

  • Pregnancy test scheduled 9-12 days post-transfer

Luteal Phase Support

Progesterone Supplementation:

  • Start: Evening of retrieval day or day after transfer

  • Options:

    • Vaginal suppositories: 200-400 mg BID-TID

    • Vaginal gel: 90 mg daily or BID

    • Intramuscular injection: 50-100 mg daily

    • Oral progesterone: 200-400 mg BID (less effective)

  • Duration: Continue until pregnancy test; if positive, continue until 8-12 weeks gestation

Additional Medications:

  • Estradiol: 2-6 mg daily (oral or transdermal) if indicated

  • Aspirin: 81 mg daily (if indicated for specific conditions)

  • Prenatal vitamins: Continue throughout

Monitoring and Follow-up

Pregnancy Testing:

  • Beta-hCG: Quantitative serum test 9-12 days post-transfer

  • Interpretation:

    • Positive: >5-10 mIU/mL (varies by lab)

    • Repeat in 48-72 hours to assess doubling

    • Expected doubling time: 48-72 hours in early pregnancy

Early Pregnancy Monitoring:

  • First ultrasound: 6-7 weeks gestational age

    • Confirm intrauterine pregnancy

    • Assess fetal heart rate

    • Rule out multiple pregnancy

  • Obstetric transfer: Usually at 8-10 weeks to OB provider

Cycle Outcome Categories:

  • Positive pregnancy test with live birth: Success

  • Positive test with miscarriage: Biochemical or clinical pregnancy loss

  • Negative pregnancy test: Failed cycle

  • Cycle cancellation: Due to poor response, over-response, or other complications

This detailed IVF protocol represents standard practice but should be individualized based on patient characteristics, clinic protocols, and physician judgment. Success rates vary by age, diagnosis, and clinic experience, typically ranging from 30-50% live birth rate per cycle for women under 35.

Male Infertility Treatment

Medical Management:

  • Hormonal therapy (for hypogonadotropic hypogonadism)

  • Antioxidants (controversial efficacy)

  • Treatment of underlying conditions

Surgical Interventions:

  • Varicocelectomy

  • Vasovasostomy or vasoepididymostomy

  • Sperm retrieval techniques (TESE, PESA, MESA)

Assisted Reproductive Technologies:

  • IUI (for mild male factor)

  • IVF with ICSI (for severe male factor)

  • Surgical sperm retrieval with ICSI

Combined Approach

Many couples require treatment addressing both male and female factors. The treatment plan should be individualized based on:

  • Age of female partner

  • Duration of infertility

  • Severity of identified factors

  • Patient preferences and resources

  • Previous treatment outcomes

V.       Medications in Infertility Treatment

Ovulation Induction Agents

Clomiphene Citrate:

  • Mechanism: Selective estrogen receptor modulator

  • Dosage: 50-150 mg daily for 5 days

  • Side effects: Hot flashes, mood changes, visual disturbances

  • Monitoring: Ultrasound, ovulation timing

  • Success rates: 70-80% ovulation, 30-40% pregnancy

Letrozole:

  • Mechanism: Aromatase inhibitor

  • Dosage: 2.5-7.5 mg daily for 5 days

  • Advantages: Better for PCOS patients

  • Side effects: Fatigue, dizziness, hot flashes

  • Monitoring: Similar to clomiphene

Gonadotropins:

  • Types: FSH, LH, hMG, recombinant FSH/LH

  • Dosage: Highly individualized based on response

  • Monitoring: Intensive ultrasound and estradiol monitoring

  • Risks: Ovarian hyperstimulation syndrome, multiple pregnancy

Metformin:

  • Mechanism: Insulin sensitizer

  • Dosage: 1500-2000 mg daily

  • Use: PCOS patients with insulin resistance

  • Side effects: GI upset, lactic acidosis (rare)

  • Benefits: Improved ovulation, reduced miscarriage risk

Hormone Replacement

Human Chorionic Gonadotropin (hCG):

  • Use: Ovulation trigger, luteal phase support

  • Dosage: 5000-10000 units IM

  • Timing: When lead follicle reaches 18-20 mm

Progesterone:

  • Forms: Vaginal suppositories, injections, oral

  • Use: Luteal phase support in ART cycles

  • Dosage: Variable based on preparation and indication

Male Fertility Medications

Gonadotropins (for hypogonadotropic hypogonadism):

  • hCG: 1500-2000 units 2-3 times weekly

  • FSH: 75-150 units 2-3 times weekly

  • Duration: 3-6 months minimum

Clomiphene Citrate (off-label):

  • Dosage: 25-50 mg daily

  • Use: Selected cases of male hypogonadism

  • Monitoring: Testosterone levels, semen parameters

Counseling and Support

Initial Counseling

  • Explain normal reproduction and factors affecting fertility

  • Discuss realistic timelines and success rates

  • Address psychological impact of infertility

  • Provide information about support groups and resources

Treatment Counseling

  • Discuss all available treatment options

  • Explain risks, benefits, and success rates

  • Address financial considerations

  • Discuss ethical considerations (especially for ART)

Ongoing Support

  • Regular follow-up during treatment

  • Counseling for treatment failures

  • Discussion of when to stop treatment

  • Referral to mental health professionals as needed

Prognosis and Success Rates

Natural Conception

  • Couples under 35: 85% conceive within 1 year

  • Couples 35-39: 75% conceive within 1 year

  • Monthly fecundity rates decline with age

Treatment Success Rates (approximate)

  • Ovulation induction: 20-30% per cycle

  • IUI: 10-20% per cycle (varies by diagnosis)

  • IVF: 30-40% per cycle (age-dependent)

  • Success rates decline significantly after age 40

Special Considerations

Age-Related Fertility Decline

  • Fertility preservation counseling for younger patients

  • Realistic counseling for patients over 40

  • Consideration of donor gametes

Recurrent Pregnancy Loss

  • Evaluation after 2-3 consecutive losses

  • Genetic, anatomic, endocrine, and immunologic testing

  • Treatment based on identified causes

Fertility Preservation

  • Cancer patients before treatment

  • Elective fertility preservation (egg/sperm freezing)

  • Ovarian tissue cryopreservation (experimental)

 

VI.  Psychological and Social Aspects

Emotional Impact

  • Infertility creates significant psychological stress for couples

  • Higher rates of anxiety and depression compared to fertile couples

  • Grief response similar to other major losses

  • Relationship stress and sexual dysfunction common

Counseling and Support

  • Referral to mental health professionals experienced in fertility issues

  • Support groups and online communities

  • Stress reduction techniques and coping strategies

  • Decision-making support regarding treatment options

 

VII.      When to Refer

Reproductive Endocrinology and Infertility (REI) Specialist

  • Failed first-line treatments

  • Complex cases requiring ART

  • Recurrent pregnancy loss

  • Suspected genetic causes

  • Advanced maternal age (≥35 years) after 6 months of trying

Other Specialists

  • Urologist for male factor evaluation and treatment

  • Reproductive psychiatrist/psychologist for counseling

  • Genetic counselor for hereditary conditions

VIII. Key Points for Clinical Practice

  1. Early evaluation is crucial, especially for women ≥35 years

  2. Both partners should be evaluated simultaneously

  3. Evidence-based treatments should be offered in a stepwise approach

  4. Lifestyle modifications are important adjuncts to medical treatment

  5. Emotional support and counseling should be integral to care

  6. Realistic expectations about success rates should be discussed

  7. Cost-effectiveness should be considered in treatment planning

  8. Patient autonomy in decision-making should be respected

 

IX.  Conclusion

Infertility is a complex medical condition requiring comprehensive evaluation and individualized treatment approaches. Success in infertility treatment depends on accurate diagnosis, appropriate treatment selection, and ongoing patient support. As reproductive technologies continue to advance, treatment options continue to expand, offering hope to couples facing fertility challenges.

X.      References

  1. Practice Committee of the American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil Steril. 2020;113(3):533-535.

  2. Zegers-Hochschild F, Adamson GD, Dyer S, et al. The International Glossary on Infertility and Fertility Care, 2017. Fertil Steril. 2017;108(3):393-406.

  3. Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile female: a committee opinion. Fertil Steril. 2015;103(6):e44-50.

  4. Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril. 2015;103(3):e18-25.

  5. Legro RS, Arslanian SA, Ehrmann DA, et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(12):4565-4592.

  6. World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: WHO Press; 2010.

  7. Practice Committee of the American Society for Reproductive Medicine. Ovarian hyperstimulation syndrome: a committee opinion. Fertil Steril. 2016;106(7):1634-1647.

  8. Practice Committee of the American Society for Reproductive Medicine. Evidence-based treatments for couples with unexplained infertility: a guideline. Fertil Steril. 2020;113(2):305-322.

  9. Hotaling J, Carrell DT. Clinical genetic testing for male factor infertility: current applications and future directions. Andrology. 2014;2(3):339-350.

  10. De Geyter C, Calhaz-Jorge C, Kupka MS, et al. ART in Europe, 2015: results generated from European registries by ESHRE. Hum Reprod Open. 2020;2020(1):hoz038.

  11. Practice Committee of the American Society for Reproductive Medicine. Role of metformin for ovulation induction in infertile patients with polycystic ovary syndrome (PCOS): a guideline. Fertil Steril. 2017;108(3):426-441.

  12. Practice Committee of the American Society for Reproductive Medicine. Fertility evaluation of infertile women: a committee opinion. Fertil Steril. 2021;116(5):1255-1265.

  13. Schlegel PN, Sigman M, Collura B, et al. Diagnosis and treatment of infertility in men: AUA/ASRM guideline part I. Fertil Steril. 2021;115(1):54-61.

  14. Practice Committee of the American Society for Reproductive Medicine. Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertil Steril. 2016;106(7):1634-1647.

  15. Niederberger C, Pellicer A, Cohen J, et al. Forty years of IVF. Fertil Steril. 2018;110(2):185-324.e5.