Approach in infertile couple Firouzeh Akbari Asbagh Prof. of Gynaecology Tehran University of Medical Sciences oct 2014

Evaluation sooner in women with irregular Introduction An infertility evaluation is usually initiated after one year In women under age 35 years Women age 35 years and older after six months Evaluation sooner in women with irregular menstrual cycles or known risk factors for infertility such as endometriosis, history of PID, reproductive tract malformations

Initial approach Both partners of an infertile couple should be evaluated for factors that could be impairing fertility Counsel the couple about the possible etiology and offer a treatment plan The clinician should not ignore the couples emotional state witch may include depression, anger, anxiety, andMaterial discord information should be supportive and informative

History The most important points are: Duration of infertility and results of previous evaluation and therapy Menstrual history (cycle length and characteristic ) Helps in determining ovulatory status Medical, surgical, and gynecology history PID thyroid disease, galactorrhea, hirsutism, pelvic, dysmenorrhea, or dyspareunia Young women who have undergone unilateral oophorectomy generally do not reduced fertility but in older women as they may develop diminished ovarian reserve sooner than women with two ovaries Obstetrical history outcome in a future pregnancy

Sexual history including sexual dysfunction and frequency of coitus Family history including family, birth defects, genetic mutations, or mental retardation Women with fragile X permutation may develop POF Personal and lifestyle history including age, occupation, exercise, stress, dieting/changes in weight, smoking, and alcohol use, all of which can affect fertility

Physical examination Physical examination should assess for signs of potential causes of infertility BMI ,secondary sexual characteristics Hypogonadotropic hypoganadism , turner syndrome Abnormalities of the thyroid gland, galactorrhea, androgen excess ( hirsutism …), PCO Endometriosis (tenderness or masses in the adenxae or posterior cul-de-sac (pouch of Douglas) Palpable tender nodules Vaginal / cervical structural abnormalities Uterine enlargement, irregularity, or lack of mobility are sings of a uterine anomaly, leiomyoma, endometriosis, or pelvic adhesive disease

Assessment of ovulatory function Laboratory assessment Mid-luteal phase serum progesterone level >3 ng/ml Urinary ovulation prediction kit ( detect LH surg) 5 to 10 % false positive and negative Daily ultrasound to follow the development of the follicle Endometrial biopsy it is not good test (too expensive or invasive uncomfortable) ASRM affirmed the lack of benefit of the endometrial biopsy in the evaluation of the infertile female and dose not recommend

Assessment of ovarian reserve Ovarian reserve can refer to diminished oocyte quality, oocyte quantity or reproductive potential Over 35 years of age and younger women with risk factors POF Day 3 FSH (advantage: cost , simple ) less than 10 mlU /ml adequate ovarian reserve Levels 10 to 15 mlU /ml borderline FSH more than 20 mlU /ml insufficient day 3 estradiol levels <80 pg/ml adequate ovarian reserve day 3 estradiol levels >80 pg/ml high cancellation rates Low pregnancy rate day 3 estradiol levels >100 pg/ml 0% pregnancy rate Clomiphene citrate challenge test (CCCT)

Antral follicle count (AFC) TVS Size (2 to 10 mm) low AFC ranging from 4 to 10 antral follicles between days two and four of a regular menstrual cycle suggests poor ovarian reserve AFC is a good predictor of ovarian reserve and response less predictive of oocyte quality the ability to conceive with IVF and pregnancy outcome

Anti- Mullerian hormone (AMH) AMH level an early, reliable, direct indicator of declining ovarian function Patients have had significant ovarian injury from radiation or surgery Patient planning IVF AMH level correlates with the number of oocytes retrieved after stimulation and is the best biomarker for predicting poor and excessive ovarian response Measured anytime during the menstrual cycle

General guidelines AMH <0.5 ng/ml predicts reduced ovarian reserve with less than three follicles in an IVF cycle AMH <1.0 ng/ml predicts baseline ovarian reserve with a likelihood of limited eggs at retrieval AMH >1.0 ng/ml but <3.5 ng/ml suggests a good response to stimulation AMH >3.5 ng/ml predicts a vigorous response to ovarian stimulation and caution should be exercised in order to avoid OHSS

Assessment fallopian tube patency& Uterine cavity HSG first -line test Water or lipid soluble contrast Abnormalities such as Submucous fibroids a T- shaped cavity, polips, synechiae, and congenital Mullerian anomalies HSG is not useful for detecting peritubal adhesions or endometriosis Abnormalities found on HSG hysteroscopy, or laparoscopy hysteroscopy definitive method for evaluation abnormalities of the endometrial cavity diagnosis and treatment Chlamydia antibodies

Hysterosalpango- contrast sonography (HyCoSy) Safe well tolerated, quick and easy method for obtaining information on tubal status the uterine cavity, the ovaries, and the myometrium using conventional ultrasound HyCoSy is a simple time –efficient and effective method for evaluation of tubal patency, the uterine cavity , and the myometrium

Role of laparoscopy The evaluation of infertility is Controversial Invasive and expensive Indication Endometriosis and adhesions/tubal disease… Laparoscopy and hysteroscopy

Test of limited clinical utility postictal test Not recommend Basal body temperature records Zona- free hamster oocyte penetration test Mycoplasma cultures karyotype