Infertility

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  • The monthly conception rate is 20% in a group of normal fertile couples.
  • Infertility with increasing age of the female partner.
  • Affects 15% of couples.
  • Female factors account for 40–50% of infertile couples. (MCQ)
  • Male factors account for 23% of infertile couples.
  • In 40% of infertile couples, there are multiple causes.
  • The inability to conceive after 12 months of unprotected sexual inter- course.
  • Types
    • Primary infertility: Infertility in the absence of previous pregnancy.
    • Secondary infertility: Infertility after previous pregnancy.
  • Evaluation of Infertile Couple
    • Multifactorial: 40%.(MCQ)
    • Unexplained: 28%.
    • Anovulation: 18%.
    • Tubal disease: 14%.
    • Endometriosis: 9%.
    • Abnormal sperm function.
    • Abnormal sperm production.
    • Obstruction of ductal system (seminiferous tubules to urethral oriface).
  • Infertility workup
    • Male factor: Semen analysis.
    • Ovulation factor: Serum progesterone, day 3 FSH, prolactin, endometrial biopsy.
    • Cervical factor: Postcoital test.
    • Uterine factor: Ultrasonography, hysterosonogram, hysterosalpingogram, hysteroscopy.
    • Tubal factor:  Hysterosalpingogram, laparoscopy.
    • Endometriosis: Laparoscopy.
  • Male Factor
    • Semen analysis
      • Performed after at least 48 hr of abstinence (MCQ)
      • examination of the sperm within a maximum of 2 hrs from time of ejaculation (for those who prefer to collect at home). (MCQ)
      • Two properly performed semen analyses should be obtained at least 4 weeks apart.
      • The analysis reflects sperm production that occurred 3 months ago. (MCQ)
      • Characteristics (A very important MCQ)
        • Volume:  Normal > 2 mL.
        • Semen count: Normal > 20 million/mL.
        • Motility: Normal > 50% with forward movement.
        • Morphology: Normal > 40%.
    • Treatment for abnormal semen analysis
      • Depends on the cause.
      • Refer to urologist.
      • Smoking and alcohol cessation.
      • Avoid lubricants with intercourse.
      • Clomiphene 25 mg/day for 25 days, with 5 days of rest (for the male partner). (MCQ)
      • Artificial insemination (with partner or donor sperm):
      • Intrauterine insemination: Sperm injected through cervix.
      • Intracytoplasmic sperm injection.
      • If semen analysis is normal, continue workup of other factors.
  • Methods of assessing ovulation
    • History of regular monthly menses is a strong indicator of normal ovulation.
      • Basal body temperature (BBT):
      • Body temperature rises about 0.5°1°F during the luteal phase due to the level of progesterone. (MCQ)
      • Elevation of BBT is a good indicator that ovulation is taking place.
    • Serum progesterone:
      • May be low if the corpus luteum is not producing enough.
    • Day 3 FSH: (MCQ)
      • Elevated if patient is anovulatory.
    • Endometrial biopsy:
      • Determines histologically the presence/absence of ovulation.
  • Possible causes and treatments of anovulation
    • Pituitary insufficiency:
      • Treat with intramuscular luteinizing hormone/ follicle-stimulating hormone (LH/FSH) or clomiphene.
    • Hyperprolactinemia:
      • Administer bromocriptine, a dopamine agonist, which supresses prolactin.
    • PCOS:
      • Treat with clomiphene +/– metformin, weight loss.
    • Other causes:
      • Hyper/hypothyroid, androgen excess, obesity/starvation, galactorrhea, stress.
    • Internal architecture study
      • analysis of uterus and fallopian tubes is performed
      • conducted if ovulation analysis and semen analysis are normal
    • Hysteroscopy:
      • A hysteroscope is an telescope that is connected to a video unit with a fiber-optic light source.
      • It is introduced through the cervix and allows visualization of the
      • uterine cavity.
      • It is diagnostic and therapeutic.
      • Hysteroscopy is useful in: (MCQ)
        • Asherman syndrome (lyse intrauterine adhesions).
        • Endometrial polyps (polypectomy).
        • Congenital uterine malformations (eg, excise a uterine septum).
        • Submucosal fibroids (resect).
    • Hysterosalpingogram:
      • Radiopaque dye is injected into the cervix and uterus.
      • Dye passes through the fallopian tubes to the peritoneal cavity.
      • It should outline the inner uterine contour and both fallopian tubes when imaged with fluoroscopy.
      • Allows visualization of uterus and fallopian tubes.
      • Performed during follicular phase (avoid possibility of pregnancy).
      • There is a risk of salpingitis from the injection.
      • An interventional radiologist can use catheters to open the fallopian tubes that are occluded proximally.
    • Sonohysterogram:
      • Fluid is instilled in the endometrial cavity concurrently with a pelvic

                   ultrasound.

      • Outlines intrauterine pathology (ie, polyps, submucosal fibroids).
      • Can be done with an ultrasound in an office setting.
    • Ultrasound:
    • Laparoscopy:
      • Can visualize outside of the uterus to assist in diagnosis of some mullerian malformations.
  • Causes and treatments for uterine factor infertility
    • Submucosal fibroid: (MCQ)
      • Resection, myomectomy.
    • Intrauterine septum: (MCQ)
      • Hysteroscopic resection of septum.
    • Uterine didelphys: (MCQ)
      • Metroplasty—a procedure to unify the two endometrial cavities.
    • Asherman syndrome: (MCQ)
      • Hysteroscopic lysis of intrauterine adhesions.
  • Causes and treatments for tubal factor infertility
    • Adhesions:
      • Lysis of adhesions via laparoscope.
      • Microsurgical tuboplasty.
    • Neosalpingostomy (blocked tubes are opened).
    • Tubal reimplantation for intramural obstruction.
    • In vitro fertilization (IVF).
    • Tubal blockage: Tubal flushing.
      • If the evaluation up to this point is within normal limits, then a diagnostic laparoscopy should be done.
    • Laparoscopy is diagnostic and therapeutic.
  • Causes and treatments for peritoneal factor infertility
    • Adhesions: Lysis of adhesions via laparoscopy.
    • Endometriosis: Excision or ablation of implants.
  • Assisted reproductive technologies (ARTs)
    • Intrauterine Insemination
      • Washed sperm is injected into the uterus.
      • Must have a normal tube for fertilization to take place.
    • In Vitro Fertilization (IVF) and Embryo Transfer
      • Egg cells are fertilized by sperm outside the uterus.
      • Consists of ovarian stimulation, egg retrieval, fertilization, selection, and embryo transfer into uterus.
      • Success rate of IVF is about 20%.
    • Intracytoplasmic Sperm Injection (ICSI)
      • Subtype of IVF.
      • Injection of spermatozoan into oocyte cytoplasm.
      • Revolutionized treatment of infertility in men with severe (MCQ)
        • Oligospermia (low number)
        • azoospermia (absence of live sperm),
        • asthenospermia (low motility),
        • teratospermia (abnormal morphology).
      • Pregnancy rate: 20% per cycle.
      • Multiple pregnancy rate: 28–38%.
      • Not influenced by cause of abnormal sperm.
      • Can use spermatozoa from testicular biopsies.
    • Gamete Intrafallopian Transfer (GIFT)
      • Egg and sperm are placed in a normal fallopian tube for fertilization.
      • Success rate is about 25%.(MCQ)
    • Zygote Intrafallopian Transfer (ZIFT)
      • Zygote created via fertilization in vitro and placed in fallopian tube, where it proceeds to uterus for natural implantation.
      • Success rate is about 30%. (MCQ)
    • Artificial Insemination with Donor Sperm
      • Success rate is 75% in six cycles. (MCQ)
      • Donor sperm is used for ARTs.

Controlled ovarian hyperstimulation and protocols for IVF

  • The agents most commonly used to stimulate multiple ovarian follicles are CC, hMG, and purified FSH.
  • Clomiphene-only regimens
    • given on days 5–9 of the menstrual cycle. (MCQ)
    • Response may be followed by BBT measurement, ultrasonography, and measurement of LH and estradiol levels
    • CC has a low risk of ovarian hyperstimulation syndrome (OHSS).
    • However, it creates a low oocyte yield (one or two per cycle) with frequent LH surges that lead to high cancellation rates in IVF cycles and low pregnancy yield.
    • Most treatment regimens start with 5(MCQ)0 mg/day for 5 days
    • If ovulation fails to occur, the dose is increased to 100 mg/day.
    • The maximum dose is 250 mg/day.
    • Human chorionic gonadotropin (hCG), 5000 IU to 10,000 IU, may be used to simulate an LH surge
    • Eighty percent of properly selected couples will conceive in the first three cycles after treatment.
    • Potential side effects (MCQ)
      • vasomotor flushes, blurring of vision, urticarial
      • pain, bloating, and multiple gestation (5–7% of cases, usually twins).
  • Clomiphene/hMG combinations
    • used to increase the number of recruited follicles
    • The hMG and purified FSH are useful in patients(MCQ)
      • who do not achieve pregnancy with CC
      • with endometriosis or unexplained infertility.
    • hMG (MCQ)
      • is a combination of LH and FSH
      • is given for 2–7 days after the clomiphene.
      • can lead to life-threatening OHSS.
    • Follicle maturation is monitored using sonography and serial measurement of estradiol levels.
    • To complete oocyte maturation, hCG needs to be given once the follicles have reached 17–18 mm in diameter. (MCQ)
    • Aspiration of follicles should be timed 35–36 hours after the hCG injection. (MCQ)
    • The disadvantages of this protocol include (MCQ)
      • premature luteinization
      • spontaneous LH surges that result in high cancellation rates
      • multiple gestations.
  • Gonadotropin-releasing hormone analogs/agonists (GnRHa)
    • used via a flare-up protocol or a luteal phase protocol.
    • flare-up protocol
      • causes an elevation of FSH in the first 4 days, which increases oocyte recruitment.
      • After 5 days of administration, the GnRH agonist then down-regulates the pituitary to prevent premature luteinization and a spontaneous LH surge(MCQ)
    • The luteal phase protocol
      • involves starting GnRHa administration on the seventeenth to twenty-first menstrual day. (MCQ)
      • GnRHa increase the number, quality, and synchronization of the oocytes recovered per cycle and thereby improve the fertilization rate, the number of embryos, and the pregnancy rate.
    • Successful ovulation rates are 75% to 85%.
    • GnRHa
      • more complex to use
      • can lead to OHSS. (MCQ)
  • GnRH analogs/antagonists
    • block LH secretion without causing a flare-up effect.
    • They are administered in a
      • single dose on the eighth menstrual day
      • in smaller doses over 4 days. (MCQ)
    • Because they block the periovulatory LH surge, fewer gonadotropins are required to stimulate ovulation, and side effects are decreased.
  • Oocyte retrieval, culture fertilization, and transfer
    • The two major techniques of oocyte retrieval are
      • ultrasonographically guided follicular aspiration
      • laparoscopic oocyte retrieval.
    • Ultrasonographically guided oocyte retrieval
      • Most widely used technique
      • Usie a 17-gauge needle passed through the vaginal fornix
      • performed 34–36 hours after hCG injection. (MCQ)
      • The procedure is done under heavy sedation.
      • Potential complications include risk of bowel injury and injury to pelvic vessels.
  • Oocyte fertilization.
    • Sperm are diluted, centrifuged, and incubated
    • 50,000–100,000 motile spermatozoa are added to each Petri dish containing an oocyte. (MCQ)
    • Fertilization is documented by the presence of two pronuclei and extrusion of a second polar body at 24 hours. (MCQ)
    • At that stage, most embryos are cryopreserved for an unlimited period, with a survival rate of 75%.(MCQ)
  • Embryo transfer
    • most commonly carried out 48–80 hours after retrieval at the four- to ten-cell stage. (MCQ)
    • In general, no more than two embryos are transferred to limit the risk of multiple gestation and to optimize pregnancy rates.
    • It is common practice to supplement the luteal phase with progesterone given by vaginal suppository, beginning the day of oocyte release and continuing into the twelfth week of pregnancy.
  • Retrieval and pregnancy results.
    • Most programs have delivery rates of approximately 20% for women under the age of 40 years who are not affected by male factor infertility. (MCQ)
    • The risk of ectopic pregnancy is 4% to 5%,
    • risk of heterotopic pregnancies is less than 1%.
    • Multiple gestation rate is approximately 30% (25% twins and 5% triplets). older women commonly use donor oocytes to improve chances of success.


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