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Infertility Dr Angelo Smith MD WHPL


Definition Failure of a couple to conceive after 1 year of regular intercourse without use of contraception Primary infertility – No prior pregnancies Secondary infertility – Prior pregnancy


Prevalence Infertility affects 10-15% of reproductive-age couples in the world. Approx. 85% of couples achieve pregnancy within 1 year Conception rate ( fecundability ) 25% conceive within 1 mo. 60% conceive within 6 mo. ’ s 75% conceive within 9 mo. ’ s 90% conceive within 18 mo. ’ s


Etiology Successful conception requires a specific series of events: Ovulation of competent oocyte Production of competent sperm Juxtaposition of sperm and oocyte in a patent reproductive tract Fertilization Generation of a viable embryo Transport of the embryo to the uterine cavity Implantation of the embryo into the endometrium


Etiology Major causes of of infertility: Female factor – 60% Ovulatory dysfunction Abnormalities of female reproductive tract Peritoneal factors Reproductive aging Male factor – 20% Abnormal semen quality Abnormalities of male reproductive tract Idiopathic – 15% Infertility in ~ 20-40% of couples has multiple causes

Infertility: History:

Infertility: History Female Duration of infertility and prior evaluation or therapy Menstrual cycle (length and characteristics) Symptoms associated with ovulation (e.g. breast tenderness, bloating, mood changes) Full OBHx and GynHx Prior pregnancies, surgeries, or STD’s Sexual history (frequency of intercourse) Chronic medical illness Family history (infertility, birth defects, genetic disorders) Social history (smoking, EtOH , drugs)

Infertility: History:

Infertility: History Male Prior children Genital tract infections Genital surgery or trauma Chronic medical illness Medications (e.g. Furantoins , CCB) EtOH , drugs, or smoking Sexual history (frequency of intercourse)

Infertility: Physical Exam:

Infertility: Physical Exam Female Height, weight , BMI Pelvic exam Masses Tenderness ( Adnexa , Cul-de-sac) Structural abnormalities (Vagina, Cervix, or Uterus) Male Evidence of androgen deficiency Structural defects (e.g. varicocele , hernia)

Male factor: Evaluation:

Male factor: Evaluation Initial evaluation Further evaluation Male Factor Semen analysis Urologic evaluation FSH, LH, and testosterone level Genetic evaluation Epididymal sperm aspiration (PESA, MESA) Testicular biopsy

Male factor: Evaluation:

Male factor: Evaluation Element Reference value Ejaculate volume 1.5-5.0 mL pH > 7.2 Sperm concentration > 20 million/mL Motility > 50% Morphology > 30% normal forms Semen analysis Following 2-4 day period of abstinence Repeated x1 for accuracy

Male factor: Evaluation:

Male factor: Evaluation Urologic evaluation Physical Exam Varicocele Congenital absence of vas deferens (CAVD) Transrectal ultrasound Vasography , Seminal vesiculography Epididymal sperm aspiration (PESA or MESA)

Male factor: Evaluation:

Male factor: Evaluation Endocrine evaluation Indication: Oligospermia (< 10million/mL) or sexual dysfunction (decreased libido, impotence) FSH, LH, testosterone Genetic evaluation Indication: Azoospermia (no sperm) CF (Cystic fibrosis) mutation Karyotype ( Klinefelter ’ s , Y chromosome deletion) Testicular biopsy Indication: Nonobstructive azoospermia Palpable vasa Normal testis volume Normal FSH/LH

Female factor: Evaluation:

Female factor: Evaluation Factor Initial evaluation Further evaluation Ovulation History and physical exam Basal body temp charting Ovulation predictor kit Mid-luteal phase progesterone level Endocrine testing Endometrial biopsy Reproductive tract (uterus or fallopian tubes) Hysterosalpingogram (HSG) Ultrasound Saline-infusion sonography Hysteroscopy Laparoscopy Peritoneal Laparoscopy Reproductive aging FSH , estradiol, or AMH

Female factor: Menstrual Cycle:

Female factor: Menstrual Cycle

Female factor: Evaluation:

Female factor: Evaluation Ovulation Initial evaluation: Basal body temp – rise for > 10 days indicates ovulation Ovulation predictor kit – detects LH surge in urine Further evaluation: Mid- luteal phase progesterone level - level > 3 ng / mL provides qualitative evidence of recent ovulation Endocrine testing (TSH, prolactin , FSH, LH, Estradiol , DHEA-S) Endometrial biopsy Not routinely performed

Female factor: Evaluation:

Reproductive tract Initial evaluation: Hysterosalpingogram (HSG) Detect uterine anomalies ( septate or bicornuate uterus, uterine adhesions, uterine leiomyoma ) Detect patency of fallopian tubes (occlusion, hydrosalpinx , salpingitis ) Ultrasound – alternative to HSG to evaluate uterus Female factor: Evaluation

Female factor: Evaluation:

Reproductive tract Further evaluation: Saline-infusion sonography (SIS) Hysteroscopy Laparoscopic chromotubation Female factor: Evaluation

Female factor: Evaluation:

Peritoneal factors Laparoscopy Endometriosis Pelvic/ adnexal adhesions Female factor: Evaluation

Female factor: Evaluation:

Reproductive aging Indications: > 35 years of age 1 st degree relative with early menopause Previous ovarian insult (surgery, chemotherapy, radiation) Smoking Poor response to ovarian stimulation Unexplained infertility Candidate for IVF Female factor: Evaluation

Slide 26:

Reproductive aging Cycle day 3 serum FSH and estradiol Abnormal ( “ diminished ovarian reserve ”) FSH > 10 IU/L Estradiol > 75-80 pg/ mL Clomiphene citrate challenge test Cycle day 10 serum FSH Serum antimullerian hormone (AMH)

Idiopathic Infertility:

Prevalence ~ 15% Factors that cannot be identified Sperm transport defects Inability of sperm to fertilize egg Implantation defects Idiopathic Infertility


Management Male Factor Avoidance of alcohol Scheduled intercourse Ligation of venous plexus for significant varicocele Intrauterine insemination (IUI) with washed sperm Intracytoplasmic sperm injection (ICSI) + IVF Donor sperm insemination

Slide 31:

Ovulation Induction (Clomid or low dose FSH) IUI (low dose FSH) IVF / ICSI (LHRH analogue, high dose FSH injections, egg collection, embryo transfer)


Anovulation Oral medications: Clomiphene citrate Dopamine agonists ( Bromocriptine ) - hyperprolactinemia Injectable medications: Gonadotropins (FSH/ hMG , hCG ) Laparoscopic “ovarian drilling ” Complications: Ovarian hyperstimulation , Multiple pregnancy Management


Reproductive tract abnormality Uterine: Myomectomy , Septoplasty , Adhesiolysis Tubal : Microsurgical tuboplasty , Neosalpigostomy Peritoneal: Laparascopic treatment of endometriosis, Adhesiolysis Idiopathic infertility Ovarian stimulation + IUI Clomiphene or gonadotropins ( hMG , hCG ) IVF Management

Management (IVF):

Used for: Severe male factor Tubal disease Couples who failed other treatments Requires Controlled ovarian hyperstimulation Retrieval of oocytes In vitro fertilization and embryo transfer Procedures IVF + embryo transfer (IVF-ET) Intracytoplasmic sperm injection + embryo transfer (ICSI-ET) Donor egg IVF + embryo transfer Management (IVF)

Intracytoplasmic sperm injection (ICSI) :

Intracytoplasmic sperm injection (ICSI) ~ 40% of IVF cycles involve insemination by ICSI

Day 2 - Day 3 Embryo Development:

Day 2 - Day 3 Embryo Development

Day 5 Embryo development:

Day 5 Embryo development

Day 5 Embryo Transfer:

Day 5 Embryo Transfer Advantages Embryo Selection Reduction in number of embryos for ET resulting in reduction in multiple gestations


Psychological The psychological stress associated with infertility must be recognized and patients should be counseled appropriately.

Egg Donation :

Egg Donation For patients with poor ovarian reserve Alternative to adoption or childlessness Success Rate ~ 50% per cycle

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