INFERTILITY

Dyah Aryani Perwitasari

Definitions
Infertility = Inability of a couple practicing frequent intercourse and not using contraception to fail to conceive a child within one year. Infertility affects 15-20% of couples, or 11 million reproductive age people in the U.S. Primary infertility denotes those patients who have never conceived. Secondary infertility indicates previous pregnancy but failure to conceive subsequently.

Incidence
80 % of the couples achieve conception if they so desire, within one year of having regular intercourse with adequate frequency (4-5 times a week). Another 10 % will achieve the objective by the end of 2 nd year. As such, 10 % remain infertile by the end of 2 nd year

Factors responsible for fertility

Healthy sperms should be deposited high in the vagina. The sperms should undergo changes and acquire motility. The motile sperms should ascend through the cervix into the uterine cavity and the fallopian tubes. There should be ovulation in females. The fallopian tubes should be patent.

Causes of infertility
Tubal pathology Male factor Ovulatory dysfunction Unexplained Cervical/other 35% 35% 15% 10% 5%

Counsel patience!
In normal young couples:
25% conceive after one month 70% conceive after six months 90% conceive by one year

Only an additional 5% will conceive in an additional 6-12 months

Fecundity and Age

In a federal survey:
Impaired fertility in women < 25y is 11.7% Impaired fertility in women > 35y is 42.1%

In another study:
74% of women < 31y conceived in one year. 54% of women >35y conceived in one year.

Our challenge: presenting data in a supportive, non-judgmental manner

Tubal/ Pelvic pathology

Congenital anomalies Tubal occlusion Evaluated by:
hysterosalpingogram laparoscopy hysteroscopy

May occur as sequelae of

PID endometriosis abdominal/pelvic surgery peritonitis

Male factor

Male factor
Male partner should be evaluated simultaneously with female Causes of male infertility:
reversible conditions (varicocele, obstructive azoospermia) not reversible, but viable sperm available (ejaculatory dysfunction, inoperative obstructive azoospermia) not reversible, no viable sperm (hypogonadism) genetic abnormalities testicular or pituitary cancer

Defective Spermatogenesis
Undescended testis Orchitis (mumps usually) Genetic factors (47 XXY) Testicular toxins (drugs, radiation) Endocrinal (thyroid dysfunction, gonadotropin deficiency) Varicocele Primary testicular failure

Obstruction of afferent duct

Obstruction of efferent duct :
Congenital
Absence of vas deferens Young's syndrome

Acquired
Infective (tuberculosis, gonorrhea) Surgical trauma (hernioraphy)

Failure to deposit sperm high in vagina

Impotency Ejaculatory failure Retrograde ejaculation Hypospadius Bladder neck surgery Psychosexual Drug related

Defect in sperm and seminal fluid

Immotile sperm (kartagener syndrome ) Oligo-astheno-tertozoospermia Low fructose content Sperm antibodies

Female factor

Ovarian factors
Anovulation or oligo-ovulation Luteal phase defect (LPD) Luteinised unruptured follicle (LUF)

Tubal factors
Defective ovum pick up Impaired tubal motility Loss of cilia Partial to complete obstruction of tubal lumen

Peritonial factors
Peritoneal adhesions Endometriosis

Uterine factors
Uterine hypoplasia Inadequate secretory endometrium Fibroid uterus Endometritis (tubercular in particular) Uterine synechiae Congenital malformation of uterus

Cervical factors
Congenital elongation of cervix Uterine prolapse Acute retroverted uterus Fault in the cervical mucus

Vaginal factors
Atresia vagina (partial or complete) Transverse vaginal septum Septate vagina Narrow introitus causing dyspareunia (pain)

Ovulatory dysfunction
Causes 15% of infertility Diagnosed by menstrual irregularities, basal body temperature charting, ovulation prediction kits, serum progesterone levels.

Ovulatory Dysfunction - 2
Causes of ovulatory dysfunction:
polycystic ovary syndrome hypothalamic anovulation hyperprolactinemia premature and age-related ovarian failure luteal phase defect (theoretical)

Polycystic Ovarian Syndrome

Oligomenorrhea/amenorrhea and hyperandrogenism Prevalence: 5%. Among women with O.D., 70% have PCOS. Clinical evidence: hirsutism, acne, obesity Lab evidence: elevated testosterone, elevated DHEA-S. Polycystic ovaries supportive, not diagnostic

PCOS: Treatment Approach

Weight loss if BMI>30 Clomiphene to induce ovulation If DHEA-S >2, clomiphene + glucocorticoid (dexamethasone) If clomiphene alone unsuccessful, try metformin + clomiphene.
Source: ACOG Bulletin, #34, Management of Infertility caused by Ovulatory Dysfunction Feb 2002.

Hypothalamic Anovulation
Low levels of GnRH, low of normal levels of FSH/ LH, low levels of endogenous estrogen. Associated factors: low BMI (< 20), highintensity exercise, extreme diets, stress. Treatment: lifestyle modification.

Hyperprolactinemia
Causes: pituitary adenoma, psych meds. Test for: pregnancy, thyroid disease. Imaging: MRI for macro vs microadenoma Treament: Bromocriptine (dopamine agonist). After correction, 80% of women will ovulate, 80% will get pregnant. Discontinue treatment once pregnancy established.

Combined factors factors both in male and female partners causing infertility
General factors advanced age of wife beyond 35 yrs, ageing reduces the fertility of male but spermatogenesis continues through out life Infrequent intercourse, lack of knowledge of coital technique and timing of coitus to utilize the fertile period (are very much common even amongst literate couples) Apareunia and dyspareunia Anxiety and apprehension Use of lubricants during intercourse may be spermicidal Immunological factors

What Can I Do?

Infertility Evaluation for the Family Doctor

History and Physical - Female

History
menarche, puberty menstrual hx preganancies, abortions, birth control dysparenunia, dysmenorrhea STDs, abdominal surg, galactorrhea Weight loss/gain Stress, exercise, drugs, alcohol, psychological

Physical
weight/BMI thyroid skin (striae? Acanthosis nigracans?) pelvic (vaginal mucosa, masses, pain) rectal (uterosacral nodularity)

History and Physical - Male

History
prior fertility medications h/o diabetes, mumps, undescended testes genital surgery, trauma, infections ED drug/alcohol use, stress underwear, hot tubs, frequent coitus

Physical
habitus, gynecomastia sexual development testicular volume (5x3 cm) epididymis, vas, prostate by palpation check for varicocele

Trouble in Paradise
Dont wait a year if:
irregular menses; intermenstrual bleeding h/o PID h/o appy with rupture h/o abdominal surgery dyspareunia age > 35 male factors

On your first visit:

Semen analysis Confirm ovulation
basal body temperature charting ovulation predictor kits (detect LH surge) consider serum progesterone on day 21 TSH and prolactin. DHEA-S if concern for PCOS. FSH & estradiol on cycle day 3 if >35y. Cervical cultures prn.

Labs:

Three months later

Hysterosalpingogram
evaluates tubal patency and uterine cavity shape noninvasive but involves a tenaculum performed by radiology with gynecology supervision diagnostic and therapeutic

Sorry, no data for...

Postcoital test endometrial biopsy immune testing for antisperm antibodies routine cervical cultures

Clomiphene citrate
Effective for anovulatory patients.
Also used in unexplained fertility, but no data to support. Most effective for women with nomal FSH and estrogen, least effective in hypothalamic amenorrhea or elevated FSH. Induces ovulation by unknown mechanism Most pregnancies occur in first 3 cycles. 80% will ovulate, 40% will become pregnant in 3 cycles.

Clomiphene - complications
7% twin gestations, 0.3% triplet gestations Miscarriage rate = 15% Birth defect rate unchanged from controls Side effects: hot flashes, adnexal tenderness, nausea, headache, blurry vision Contraindications: pregnancy, ovarian cysts.

Clomiphene - Administration
50 mg po qd, cycle day 3 through 7. Induce bleeding first with progesterone if amenorrheic. Intercourse QOD cycle days 12 - 17. Track ovulation with BBT or ovulation detection kits. Increase dose to 100 qd, then 150, if no ovulation occurs.

Bibliography
Bradshaw, Karen. Evaluation and Management of the Infertile Couple. Ob/Gyn vol 5, chapter 50, 1998. Penzias, Alan. Infertility: Contemporary office-based evaluation and treatment. Obstet& Gynecol Clinics, vol 27, no 3, Sept 2000. ACOG Practice Bulletin. Management of Infertility Caused by Ovulatory Dysfunction. Number 34, February 2002. Royal College of Obstetricians and Gynecologists, The Management of

Infertility in Secondary Care: National Evidence-Based Clinical Guidelines.

www.rcog.org.uk.

Case 1
A 24 year old couple comes to see you. They have been trying to get pregnant for 8 months.
What questions do you ask?

Case 1
The woman tells you she has never been pregnant. She has a regular 28 day cycle and bleeds for 4 days each month. Her medical history is unremarkable except she got really sick when she was 16 and had nasty stuff coming from down there
what do you do next?

Case 2
A 35 year old woman and her 31 year old male partner come to see you. They have been trying to get pregnant for 6 months.
What do you ask?

Case 2
She says her periods have been irregular since she went off the pill a year ago. She has never been pregnant. He has fathered a child by another woman several years ago.
What do you look for on exam? What lab tests do you order today? Do you give them homework?

Case 2
They come back 3 months later with BBT charts showing no discernable pattern. Lab tests, including semen analysis, were all normal.
What is the diagnosis? What do you do next?

Case 2
You begin discussion of clomiphene. They want to know the side effects, and if this means theyll have sextuplets and get a free house like the folks on TV.
What do you tell them? How do you administer the clomiphene?

Case 2
They come back in one month. She feels like a total bitch - excuse me, doctor on the clomiphene. She is not pregnant. BBT charting shows a mid-cycle temperature rise.
What happens next?