Diagnosis of Infertility Fecundability - the probability of conception occurring in a population of couples in a given period of time usually 1 month -normal

monthly fecundability is 2.0 Time of Exposure 3 months 6 months One year Two years % Pregnancy 57 72 85 93

Infertility -failure to conceive after frequent unprotected intercourse for 1-2 years Primary- if the woman has never been pregnant Secondary- if it occurs after one or more pregnancies Indications for Earlier Evaluation and Treatment Age 35 and over History of oligomenorrhea/amenorrhea Known or suspected uterine/pelvic/tubal pathology/endometriosis Partener known to be subfertile Causes of Infertility in Couples Tubal and pelvic- 35 Male- 35 Unexplained- 10 Unusual- 5 Diagnostic Evaluation Semen analysis Hormonal evaluation Ultrasound Hysterosalphingogram Hysteroscopy Laparoscopy Semen Analysis -cornerstone of male fertility evaluation -abstinence for 2-5 days -collected in a sterile container -delivered and examined within 30 minutes -sample should be kept at body temperature

Criteria Volume Liquefaction time pH Sperm concentration

Reference Value 2.0 mL or more Within 60 minutes 7.2 or more 20 M/mL or more

Total sperm number Motility Morphology Vitality WBC

40 M per ejaculate 50% or more motile sperm 30% or 15% 75% or more alive <1 M/mL

Basic semen analysis using WHO criteria -good sensitivity; poor specificity -repeat semen Semen analysis at least 2 weeks apart if abnormal; repeat after 3 months if normal Hormonal Evaluation FSH LH Prolactin TSH Ultrasound -initial evaluation of the pelvis -uterine pathology- myoma; endomyosis -sonhystography- highly sensitive method to diagnose intrauterine abnormalities -pelvic pathology- endometriomas -follicle monitoring; presumptive evidence of ovulation Hysteroscopy -gold standard in the diagnosis and management of intrauterine abnormalities -direct visualization of the endometrial cavity -costly and invasive; reserve for evaluation and treatment of abnormalities defined by less costly method -(+) fluoroscopy/ selective tubal cannulation to confirm or exclude proximal Hysterosalphingogram -defines the size and shape of endometrial cavity -reveal congenital anomalies (unicornuate, septate, and bicornuate uteri) -other acquired abnormalities (myoma, polyp, synechiae) -standard method for evaluating pregnancy -water and lipid -Contraindications Possible pregnancy Abnormal bleeding of unknown origin Acute PID Recent curettage -risk of infection is 4%, prophylactic antibiotics should be considered if there is history of PID, septic abortion or endometriosis Laparoscopy -final diagnostic procedure -Direct visualization of the pelvis -diagnosis of unrecognized pelvic factors e.g. endometriosis, pelvic adhesions -(+) chromotubation to demonstrate tubal patency or document tubal occlusion in cases where HSG is non occlusive -Indications: Unexplained infertility

Suspected case of endometriosis HSG suggestive of _____

Ovulatory Dysfunction -identified in 15% of all couples and accounts for up to 40% of infertility in woman -wide range of menstrual disturbances Fertility and Age -fertility diminishes with age -infertility in general population is 14% -by age group: 5.5% at 25-29 years 9.4% at 30-34 years 19.7% at 35-39 years -with regular unprotected intercourse Ovarian Reserve -day 3 FSH and estradiol -elevated D3 FSH have been correlated with diminished ovarian reserve -values less than 10 mIU/uL ( with estradiol levels less than 40 mg/mL) represents normal follicular potential -values <15 mL mIU/ mL reflect poor future reproductive failure Evaluating ovulatory function 1. check historical character of menses regular cycles occurring at 21-35 days intervals. -PMS symptoms - dysmenorrhea 2. Basal Body Temperature normal BBT should have a biphasic curve with a elevation of 0.4 degrees for 12-15 days. - 20% on monophasic BBTs are still ovulatory. - R: use is not recommended because does not reliably predict ovulation. (NICE Guidelines, 2004) 3. Urinary Leutinizing Hormone - commercial ovulation prediction kits. - Identify the mid cycle LH surge; provide indirect evidence of ovulatory funvtion. - Defines the interval in which conception is most likely. - Accuracy, reliability and cease of use vary among products. 4. Serial Transvaginal Ultrasoud - Can reveal the size and the number of developing follicle. 5. Serum Progesterone Level - Measure s serum progesterone levels during mid luteal phase. - Values more than 6 ng/ml is presumptive evidence of ovulation. - Values of more than or equal to 10 ng/ml are suggestive of normal progesterone production. - Measure serum progesterone level during the mid luteal phase. Endometrial Biopsy - Histologic evaluation demonstrating secretory endometrial development resulting from the action of progesterone, thus implying ovulation POLYCYSTIC OVARIAN SYNDROME - Most common cause of chronic anovulation. - Chronic anovulation oligo/amenorrhea - Physical and/or biochemical signs of hyprandrogenism.

Polycystic ovary on ultrasound

Hypothalamu s GnRH Pituitary LH FSH

Ovary Granulosa cells Aromatizatio n Theca cells Androge ns 5 alpha reduction 5 alpha androgens

Estrogen

Hyperandrogenic states -Chushings disease; Cushings Syndrome -congenital adrenal hyperplasia -functioning ovarian tumors (e.g. thecomas) -exogenous sources HYPERANDROGENISM - FSH and LH - Total serum testosterone - DHEA-S - 17-hydroxyprogesterone - Fasting and 2-hour post 75 gram blood glucose values - Fasting lipid panel total cholesterol, HDL, LDL triglycerides Ovulatory Dysfunction (READ) Hypothyroidism o Thyroid dysfunction can lead to menstrual dysfunction and ovulatory disorders associated with infertility Abnormal thyroid function test reported in 1.5-3.5....

HYPOTHALAM

` LH FSH

PITUITAR Y TSH

OVARY

estrogen progesteron e

THYROID GLAND

HYPERPROLACTINEMIA results in galactorrhea, irregular menses, possible infertility incidence in infertile ovulatory women range from 3.8-11.5% HYPOTHALAM prolact in (-) GNR H LH FSH OVARY PITUITAR Y prolact in BREA ST dopamin e

Uterine Causes: estrogen milk - found in 10-15%progesteron of women seeking treatment for fertility problems e Congenital Anomalies - mullerian anomalies e.g. didelphys, bicornuate etc. - incidence 2-3% of the general population - more common in women with recurrent pregnancy losses Leiomyomas - directly or indirectly associated with 5-10% of infertility cases - mechanism by which myomas may affect infertility - alter anatomic relationship between the ovary and fallopian tube disrupting ovarian pick-up and transport - interfere with normal uterine contractions imparing sperm and possibly embryo transport & transplantation - large myomas may increase the distance the sperm tried to travel - compress and dilate vasculature causing abnormal endometrial maturation or limit blood -cause thinning and atrophy of the endometrial lining overlying the myoma

Endometrial polyps - localized overgrowth of the endometrium - associated with wide range of bleeding patterns - may obstruct tubal ostia and cervical canal - affect sperm and embryo transport

Ultrasound saline infusion Tubal Disease Accounts for 14% of infertility in women Tubal obstruction and pelvic adhesions due to infection, endometriosis and previous surgery Tests for Tubal Patterns Hysterosalpingogram Not a reliable indicator for tubal Laparoscopy with chromotubation? Tubal pathology detected at laparoscopy has a strong effect on future fertility compared to HSG

PELVIC CAUSES Endometriosis 25-50% of women with endometriosis are infertile infertile women are 6-8 more likely to have endometriosis compared to fertile women monthly fecundity in women with endometriosis is 0.02-0.10 compared to 0.150.20 of normal couples Biologic Mechanism Distorted pelvic anatomy (READ) follicle syndrome Impaired implantation Disorders of endometrial function Ultrasound CT scan Laparoscopy MALE INFERTILITY Account for infertility in 35% of couples Semen analysis cornerstone in the diagnosis of male infertility 1. Oligospermia abnormal count 2. Asthenospermia abnormal motility 3. Teratospermia abnormal morphology 4. Azoospermia absence of sperms in the ejaculate 5. Aspermia absence of sperms + ejaculate

ETIOLOGIC FACTORS Coital Disorders Erectile dysfunction - psychosexual - endocrine, neural or vascular Ejaculatory failure - psychosexual - after genitourinary surgery - neural - drug related Post testicular Obstructive - epididymis congenital - infective vasal genetics- cyctic fibrosis acquired vasectomy - Epididymal motility

Accesory gland inf? Immunologic Idiopathic Post vasectomy Etiologic Factors in Male Infertility Testicular 1. genetic klinefelters syndrome X chromosome deletions Immotile cilia syndrome 2. congenital cryptochordism 3. infective (orchitis) 4. anti- spermatogenic agents heat chemotherapy drugs, irradiation 5. vascular torsion varicocele 6. immunologic 7. idiopathic Unexplained infertility Yield normal results 10-15% of infertile couples; <10% after normal findings on laparoscopy. MANAGEMENT OVULATION INDUCTION Clomiphene Citrate

MOA binds to estrogen receptors falsely lowering true estrogen signal elevated FSH and estrogen Anti-estrogenic effect on the uterus,cervix and vagina. Started at 50 mg a day X5 days and increased at increments of 50 mg. Human menopausal gonadotropin Recombinant FSH/LH GnRH OVARIAN HYPERSTIMULATION SYNDROME Exaggerated response to ovulation induction, self limiting disorder Hallmark : increase incapillary permeability resulting in fluid shift from intracellular space to 3rd space compartment, angiotensin-mediated. Increase secretion or exudation of protein rich fluid from the ovaries and peritoneal surface. Increase follicular fluid levels of rennin and prorenin. Treatment: supportive; prevent hemodynamic collapse.

Management o Endometriosis ---------Surgical-laparoscopy vs ex-lap COH + IUI, no room for medical mx. o Myoma------------------ Surgery o Tubal Disease----------Surgery, IVF o Male factor ------------Medical/surgical + IU/IVF Management Assisted Reproductive Techniques (HRT) o Are procedures that involve the handling of oocytes and embryos outside the body, with gametes or embryos replaced into the body to establish pregnancy. In vitro fertilization (IVF) Intra- cytoplasmic sperm injection (ICSI) Intracytoplasmic sperm injection (GIFT) Zygote intrafallopian transfer (ZIFT) Tubal Embryo Stage Transfer (TEST) Indications for IVF Severe endometriosis Severe irreparable tubal occlusion Severe male infertility Failed artificial insemination Indications for ICSI Surgically retrieved sperms Repeated fertilization failure after conventional IVF Ejaculatory disorder OAT syndrome Antisperm antibody OBSTRUCTIVE AZOOSPERMIA SPERM RETRIEVAL TECHNIQUES

Testicular sperm aspiration or Extraction (TESA and TESE); for non-obstructive azoospermia. Microsurgical epididymal sperm aspiration (MESA); vasa epididymostomy Percutaneous epididymal sperm aspiration (PESA); method of choice in irreparable obstructive azoospermia.