Infertility INA S. IRABON, MD, FPOGS, FPSRM, FPSGE OBSTETRICS AND GYNECOLOGY REPRODUCTIVE ENDOCRINOLOGY AND INFERTILITY
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Reference Comprehensive Gynecology 7 th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 42, Infertility; pp 897-923
Outline Definition Causes of infertility Diagnostic evaluation Treatment
Infertility : definiti0n Inability of a couple to conceive after 1 year of trying. After 6 months, if: Ø> 35 years old Øoligo/amenorrhea Øknown tubal obstruction Øuterine disease Øsevere endometriosis Ø known male factor
Infertility approximately only 50% of the couples will conceive in 3 months, 75% will conceive in 6 months, and by 1 year approximately 90% will have conceived
Infertility : definiti0n fecundability monthly conception rate: 20% for normal couples impaired fecundity - a more general term applying to all women who have difficulty conceiving or carrying a pregnancy to term Unexplained infertility no specific diagnosed cause of infertility
Infertility Data from both older and more recent studies have indicated that the percentage of infertile couples increases with increasing age of the female partner
Infertility: Causes ovulatory disorders : 27% Male factors: 25% Tubal disorders: 22% Endometriosis: 5% other: 4% unexplained factors:17%.
Diagnostic Evaluation
Review: Menstrual Physiology E peak à Ovulation:24h LH surge à ovulation:12-16h PSREI Midyear Convention May 11 2015
1. Couple s Medical History type of infertility (primary or secondary) and its duration History of previous pregnancies and their outcomes; History of previous infertility evaluation/treatment Female menstrual history Male medical history
1. Couple s Medical History Couple s history of sexually transmitted diseases (STDs); surgical contraception (eg, vasectomy, tubal ligation); lifestyle; consumption of alcohol, tobacco, and recreational drugs (amount and frequency); occupation; and physical activities History of abdominal or pelvic surgery History of chemotherapy or radiation Couple s current medical treatment (if any), reason, and any history of allergies Complete review of systems to identify any endocrinologic or immunologic issue that may be associated with infertility
2. Couple s Physical Examination Vital Signs Height/weight Head and neck assessment Breast evaluation Abdominal evaluation Dermatologic evaluation
2. Couple s Physical Examination Thorough gynecologic evaluation Speculum examination Bimanual examination Extremities evaluation
2. Couple s Physical Examination The urologist usually examines the male partner if the patient's history of his semen analysis produces an abnormal finding. Attention should be directed to congenital abnormalities of the genital tract (eg, hypospadias, cryptorchid, congenital absence of the vas deferens). Testicular size, urethral stenosis, and presence of varicocele are also determined. A history of previous inguinal hernia repair can indicate an accidental ligation of the spermatic artery
3. Documentation of Ovulation History of regular monthly cycles LH kits ( ovulation kits ) Mid luteal serum progesterone > 10 ng/ml (some books: 3 ng/ml) BBT (basal body temperature) Endometrial biopsy Ultrasound/ follicle monitoring Pregnancy the best evidence of ovulation Progesterone dependent
Basal body temperature (BBT) Indirect evidence that ovulation has taken place Provides information about the approximate day of ovulation and duration of the luteal phase. Temp should be taken shortly after awakening, only after at least 6 hours of sleep and prior to ambulating, with sublingual placement of a special thermometer with gradients between 96 o F and 100 o F!"#$%&!'(: *+,-./+0 1%&&2'3 Anovulatory: MONOPHASIC
Urinary Luteinizing hormone determination/ LH Kits / Ovulation kits Identifies midcycle LH surge Provides indirect evdence of ovulation Helps define interval of greatest fertility: the day of LH surge and the next day Best done using midday urine specimen
Also called endometrial dating Endometrial biopsy Indirect evidence of ovulation: secretory endometrium NO LONGER RECOMMENDED as part of infertility evaluation!
Ultrasound/ Follicle Monitoring Direct evidence of ovulation Corpus luteum: evidence of ovulation Usually done every other day from day 10/12
Ultrasound Can detect significant pathology such as fibroids, endometriosis, polycystic ovaries and other pathology that can possible affect fertility. Can be used to determine antral follicle count (AFC, cycle days 2-4) in the assessment of ovarian reserve.
4. Ovarian Reserve tests Not be routinely done for infertility patients Done only for female patients who are/have: 1. 35 years old and above 2. History of pelvic or ovarian surgery 3. History of chemotherapy 4. Family history of early menopause/premature ovarian failure 5. History of poor response to infertility treatment 6. Planning to undergo ART/IVF
4. Ovarian Reserve Tests a) Day 3 FSH (NV: < 10 IU/ml) b) Day 3 Estradiol (NV < 80 pg/ml) c) Clomiphene citrate challenge test d) Antral follicle count/afc
4. Ovarian Reserve Tests e) AntiMullerian Hormone/AMH f) Inhibin
5. Tubal Patency tests Chromotubation (thru exploratory lap/ laparoscopy) Hysterosalpingogram (HSG) Sonohysterosalpingogram/saline infusion sonohysterogram (SISH)
Hysterosalpingogram
6. Post coital test (PCT) Sims-Huhner test A normal PCT is one in which at least five motile sperm are visible in normal cervical mucus obtained from the upper canal just prior to ovulation May be done as an alternative to semenanalysis
8. Semen analysis The male partner should be advised to abstain from ejaculation for 2 to 3 days before collection of the semen sample, because frequent ejaculation lowers seminal volume and possibly, the sperm count. It is important that the entire specimen be collected, because the initial fraction contains the greatest density of sperm. Parameters used to evaluate the semen include volume, viscosity, sperm density, sperm morphology, and sperm motility
8. Semen analysis
8. Semen analysis In case of poor semen quality: it is best to repeat the test at least once if an abnormality is found. f abnormalities persist, the male should have a urologic exam. comprehensive evaluation should include: a history and physical exam (occasionally with ultrasound); hormonal evaluation (LH, follicle-stimulating hormone, testosterone, estradiol, prolactin, and thyroid-stimulating hormone); genetic abnormalities (karyotype, and defects such as cystic brosis mutations and Y-chromosome microdeletions), particularly with severe sperm abnormalities
9. Chlamydia antibody titers (CAT) if elevated may signify the possibility of tubal disease. If the immunoglobulin G (IgG) antibody titer is greater than 1:32, 35% of patients have evidence of tubal damage
10. Other tests The following additional laboratory procedures have been advocated by some to assist in determining the cause of the infertility: (1) measurement of serum TSH and prolactin levels in ovulatory women, if not already done; (2) luteal phase endometrial biopsy; (3) measurement of antisperm antibodies in the male and female partner; (4) bacteriologic cultures of the cervical mucus and semen; (5) other sperm testing, such as hypoosmotic swelling, hamster egg penetration test, and DNA fragmentation.
Treatment
Anovulation Ovulatory drugs 1. Clomiphene citrate 2. Aromatase inhibitors 3. Gonadotropins Laparoscopic ovarian drilling (LOD)
Anovulation If with hypothyroidism à correct thyroid disorder If with hyperprolactinemia à bromocriptine
Clomiphene citrate and aromatase inhibitors Clomiphene citrate Aromatase inhibitors
Gonadotropins indicated for ovulation induction when estrogen levels are low and when there is no repose to CC or letrozole. Low serum E2 levels (usually <30 pg/ml) or lack of withdrawal bleeding after progestogen administration signifies a state that will be unresponsive to oral therapies (CC, letrozole) use gonadotropins when there is resistance to CC or letrozole. Gonadotropins have also been used when there has been the inability to conceive after several (four to six) cycles of CC or letrozole, although this indication is not as frequently applied today.
Laparoscopic ovarian drilling/ovarian diathermy a possible alternative to gonadotropin therapy in clomiphene-resistant women with PCOS Laparoscopic electrical or lasergenerated burn holes through the ovarian cortex have been associated with improving ovulation rates major advantage of this more invasive method of ovarian electrocauterization is that it decreases the risk of hyperstimulation and multiple pregnancies. In addition to a concern of surgical complications, excessive destruction of the ovarian cortex can lead to premature ovarian failure. Only a limited number of burn holes ( 10) should be made.
Weight and lifestyle management Particularly in women who are clomiphene-resistant, weight loss will often ameliorate the situation. In overweight women, it is important to ensure that abnormalities in glucose and lipid metabolism are normalized as much as possible, before induction of ovulation. lifestyle changes in diet and exercise may improve overall fitness and metabolic parameters, as well as ovulatory responses
Tubal block Tubal surgery In vitro fertilization (IVF)
Male factor infertility History, physical exam Semen analysis 2 Normal Abnormal Female evaluation Hormone evaluation Eliminate gonadotoxins Abnormal Normal Not improved Improved Treat female factor Unexplained infertility: antisperm antibodies; DNA integrity; sperm penetration or hemizona assay Further evaluation based on semen analysis Treat female factor Low volume Oligospermia, asthenospermia Azoospermia Figure 42.18 General algorithm for the diagnostic evaluation of male infertility. (From Turek PJ. Practical approaches to the diagnosis and management of male infertility. Nat Clin Pract Urol. 2005;2:226-238.) as testicular abnormalities and infection (Fig. 42.18). The more
Male factor infertility Life-threatening problem? Treat Correctable problem? Yes Maternal reproductive potential >1 year? No Genetic evaluation Yes Correct male factor: varicocele, obstruction, hormone abnormality, infection, exposure No IUI, IVF IVF-ICSI Figure 42.19 General algorithm for treatment of male infertility. ICSI, Intracytoplasmic sperm injections; IUI, intrauterine insemination; IVF, in vitro fertilization. (From Turek PJ. Practical approaches to the diagnosis and management of male infertility. Nat Clin Pract Urol. 2005;2:226-238.)
Male factor infertility Testicular surgery (?) Urology Intrauterine insemination (IUI) IVF
Unexplained infertility Ovulation induction +/- IUI IVF
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