Definition.
Infertility is defined as the failure of a couple of reproductive age to
conceive after at least 1 year of reg...
• Epidemiology
Infertility affects about 10% to 15% of
reproductive–age couples in the Unite States.
Half of them (8%) wil...
Differential Diagnosis .
The differential diagnoses of infertility encompass five principal
categories:
1-male factors,
2-...
Differential diagnosis Percent Basic evaluation
Male factors 30 Semen analysis
Tubal/uterine/peritone
al factors
25 Hyster...
Evaluation
the infertility evaluation comprises eight major
elements:
(a) history and physical examination;
(b) semen anal...
• After the completion of these steps outlined ,
no abnormality or cause of infertility can be
identified in 10% to 15% of...
• A-History and Physical Examination. The initial
assessment begins by obtaining an extended and
complete history from bot...
• The history from the male partner should cover
any pregnancies previously sired; any history of
genital tract infections...
• The normal location of the urethral meatus
should be ensured. Testicular size should be
estimated by comparison with a s...
Exclusion of Male Factor Infertility. The cornerstone of male factor
infertility evaluation is the semen analysis. The sem...
Table: Reference values for semen analysis
Parameter Normal value
Volume 2.0 ml or more
PH 7.2-7.8
Sperm concentration 20 ...
B- Exclusion of Cervical Factor Infertility.
The postcoital test (PCT) or Huhner's test allows direct analysis of
sperm an...
The most common cause of an abnormal PCT is
poor timing. Other causes include cervical stenosis,
hypoplastic endocervical ...
C- Exclusion of Ovulatory Factor Infertility
To exclude ovulatory dysfunction, the presence of
ovulation must be confirmed...
Confirmation of Ovulation
1-The basal body temperature (BBT) chart is a simple means of
determining whether ovulation has ...
2-Midluteal phase progesterone level is another test to assess
ovulation. A concentration greater than 3.0 ng/mL in a bloo...
Assessment of Ovarian Reserve
Depleted ovarian reserve adversely impacts fecundability given
the inferior quantity and qua...
Clomiphene citrate challenge test (CCCT):
The administration of clomiphene citrate 100 mg orally on
menstrual cycle days 5...
D- Exclusion of Structural Factors (tubal blockage)
The hysterosalpingogram (HSG) assesses uterine
and fallopian tube cont...
As more dye is injected, the dye passes through the
uterine cavity into the fallopian tubes and
peritoneal cavity. X-ray f...
A diagnostic laparoscopy assesses peritoneal and
tubal factors, such as endometriosis and pelvic
adhesions, and can provid...
Dye (usually a dilute solution of
indigo carmine) should be instilled through
the fallopian tubes (chromopertubation)
duri...
. Treatment
1-Anovulation. The WHO stratifies anovulatory women into three
classes:
WHO Class I: Hypogonadotropic hypogona...
The vast majority of anovulatory women of reproductive
age fall into WHO class II and, fortunately, this class proves
res...
CC is useful in women with oligomenorrhea and
amenorrhea, with intact hypothalamic-pituitary-ovarian
axes. Patients who ar...
2-Hyperprolactinemia.
to induce ovulation in patients with hyperprolactinemia the use of the
dopamine agonists bromocripti...
3-Other, Thyroid problems should be treated
appropriately because both hypothyroidism and
hyperthyroidism may lead to infe...
4-Male Factor Infertility. Although the gynecologist does not
directly treat male patients, therapies to treat male factor...
The initiation of intracytoplasmic sperm
injection (ICSI) has revolutionized treatment
of male infertility. As long as via...
3- Endometriosis, the ectopic growth of hormonally
responsive endometrial tissue, may account for 15% of
infertility in wo...
If pregnancy fails to occur after surgical treatment, the patient
should be directed to an infertility specialist for poss...
4-Luteal phase defects occur in both fertile and
infertile women, and treatment is highly
controversial. Nevertheless, in ...
5-Uterine factors, such as submucous leiomyomas,
intrauterine synechia (Asherman's syndrome), and
uterine deformities or s...
Ureaplasma urealyticum and Mycoplasma
hominis have also been implicated, and, if
positively identified by culture, they sh...
6-Tubal factor infertility has become more prevalent with the
increased incidence of salpingitis. The frequency of tubal
o...
Tubal spasm may mimic proximal obstruction,
however, and obstruction should be confirmed by
laparoscopy. Treatment consist...
Assisted Reproduction
Technology
38
Definition of ART
• ART refers to all techniques involving direct
retrieval of oocytes from the ovary
• ART procedures inc...
Abbreviations used in assisted conception
• IVF In-vitro fertilization
• DI Donor insemination
• GIFT Gamete intrafaillopi...
Controlled Ovarian Hyperstimulation (COH)
and Protocols for In Vitro Fertilization.
The agents most commonly used to stimu...
1-Clomiphene-only regimens
are generally given on days 5 to 9 of the menstrual cycle. Response may
be followed by BBT meas...
2-Gonadotropin regimens
increase the number of recruited follicles in patients who do not achieve
pregnancy with CC and in...
To complete oocyte maturation, hCG is administered
once the follicles have reached 17 to 18 mm in
diameter. Potential disa...
3-Gonadotropin-releasing hormone
analogs/agonists (GnRHa) are used via a flare-up
protocol or a luteal phase protocol.
The...
Oocyte Retrieval, Culture Fertilization, and Transfer
The two major techniques of oocyte retrieval are
1-ultrasonographica...
Oocyte Fertilization. Sperm are diluted,
centrifuged, and incubated before 50,000 to
100,000 motile spermatozoa are added ...
Embryo transfer is most commonly carried out 72 hours after
retrieval at the 4- to 10-cell stage. In general, no more than...
. Maternal, Fetal, and Long-Term Effects of ART
Ovarian Hyperstimulation Syndrome (OHSS). Although commonly
self-limited, ...
Prevention of suspected impending OHSS can be achieved by
lowering or withholding the hCG triggering dose, postponing
embr...
. Preimplantation Genetic Diagnosis (PGD)
•whereby parents could prevent the transmission of
genetic disorders to their of...
•PGD s used in the following
•Single-Gene Disorders. PGD is used for multiple
indications. Using the polymerase chain reac...
• Aneuploidy Testing. Fluorescence in situ hybridization (FISH) is a
molecular technique predicated on the identification ...
Who is eligible for ART
• Women with tubal diseases
• Unexplained infertility
• Endometriosis
• Immunologic causes for inf...
Methodology of ovulation induction
• The success of ovulation induction in
achieving a pregnancy is highly variable. It
de...
Improving SPA
• Sperm penetration assay (SPA) is a multi-step
laboratory test that offers a biological
assessment of human...
Other techniques
• ZIFT
• GIFT
• TEST
• POST
• ICSI
• TESE
• MESA
Abdulkareem Sultan Al-Olama 57
Other techniques Cont’d
• ZIFT
– Zygote Intrafallopian Transfer. ZIFT may be recommended if the
husband has severe male fe...
Other techniques Cont’d
• GIFT
– Gamete intrafallopian transfer was developing in 1984 as a
variation of in vitro fertiliz...
Other techniques Cont’d
• TEST
– Tubal Embryo Transfer; the placing of cleaving
embryos into the fallopian tube.
• POST
– ...
Other techniques Cont’d
• ICSI
– Intracytoplasmic sperm injection, or ICSI, was developed to treat
couples who previously ...
Other techniques Cont’d
• TESE
– Testicular Sperm Extraction
• MESA
– Microsurgical Epididymal Sperm Aspiration
62
Success rates
"take home baby rate"
• One of the first questions that most people ask is "what is the
chance for success?"...
Success rates Cont’d
• Success varies with many factors, including the number of
embryos that are transferred.
• If one em...
Success rates Cont’d
• The major hurdles to success are implantation after embryo
transfer and early pregnancy loss. The r...
Success rates Cont’d
• Twins occur in about 25% of ART pregnancies versus 1-2%of
spontaneous pregnancies. The risk of more...
67
Gynecology 5th year, 6th & 7th lectures (Dr. Hanaa)
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Gynecology 5th year, 6th & 7th lectures (Dr. Hanaa)

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The lecture has been given on Oct. 25th & 27th, 2010 by Dr. Hanaa.

Published in: Health & Medicine

Gynecology 5th year, 6th & 7th lectures (Dr. Hanaa)

  1. 1. Definition. Infertility is defined as the failure of a couple of reproductive age to conceive after at least 1 year of regular coitus without contraception.  Primary infertility exists when a woman has never been pregnant.  Secondary infertility occurs when a woman has a history of one or more previous pregnancies. Fecundability is the probability of achieving a pregnancy within one menstrual cycle. For a normal couple, this is approximately 25%.
  2. 2. • Epidemiology Infertility affects about 10% to 15% of reproductive–age couples in the Unite States. Half of them (8%) will subsequently conceive without the need for specialist advice and treatment. Of the remaining 8% who require input from fertility clinics, half (4%) comprise couples with primary infertility (no history of a previous pregnancy) while the other half have secondary infertility (difficulties in conceiving after an initial pregnancy).
  3. 3. Differential Diagnosis . The differential diagnoses of infertility encompass five principal categories: 1-male factors, 2- cervical factors, 3- ovulatory dysfunction, 4- problems with the uterus or female pelvic organs or both, 5- unexplained causes. In addition, immunologic factors that involve antiovarian or antisperm antibodies may adversely affect fertility by impairing fertilization, destroying gametes, and interfering with embryo cleavage or implantation.
  4. 4. Differential diagnosis Percent Basic evaluation Male factors 30 Semen analysis Tubal/uterine/peritone al factors 25 Hysterosalpingogram, laparoscopy, chromopertubation Anovulation/ovarian factors 25 Basal body temperature chart, midluteal progesterone level, endometrial biopsy, luteinizing hormone testing Cervical factors 10 Postcoital test Unexplained infertility 10 All of the above
  5. 5. Evaluation the infertility evaluation comprises eight major elements: (a) history and physical examination; (b) semen analysis; (c) spermatic cervical mucus interaction (postcoital testing); (d) assessment of ovarian reserve; (e) tests for occurrence of ovulation; (f) evaluation of tubal patency; (g) detection of uterine abnormalities; (h) determination of peritoneal abnormalities.
  6. 6. • After the completion of these steps outlined , no abnormality or cause of infertility can be identified in 10% to 15% of couples. This group comprises a category known as (unexplained infertility).
  7. 7. • A-History and Physical Examination. The initial assessment begins by obtaining an extended and complete history from both partners and performing a physical examination. A sexual history should include the frequency and timing of intercourse, as well as information regarding menstruation, impotence, dysparonia, the use of lubricants, and sexually transmitted diseases. Additionally, modifiable lifestyle factors that potentially reduce fecundability should be probed. They include tobacco use, alcohol or caffeine consumption, body mass index, exercise habits, and indices of stress.
  8. 8. • The history from the male partner should cover any pregnancies previously sired; any history of genital tract infections, such as prostatitis or mumps orchitis; surgery or trauma to the male genitalia or inguinal region (e.g., hernia repair); and any exposure to lead, cadmium, radiation, or chemotherapeutic agents. Excessive consumption of alcohol or cigarettes or unusual exposure to environmental heat should be elicited. Some medications such as furantoins and calcium channel blockers reduce sperm quality or function
  9. 9. • The normal location of the urethral meatus should be ensured. Testicular size should be estimated by comparison with a set of standard ovoids. The presence of a varicocele should be elicited by asking the patient to perform Valsalva's maneuver in the standing position. Rectal massage of the prostate and seminal vesicles should bring forth sufficient secretions at the urethral meatus to allow microscopic examination for white blood cells.
  10. 10. Exclusion of Male Factor Infertility. The cornerstone of male factor infertility evaluation is the semen analysis. The semen sample should be collected after a period of abstinence of at least 48 hours and is best evaluated within 1 hour of ejaculation. Additionally, the sample is graded for percent motility, sperm agglutination, and viscosity. If abnormalities are present, the patient should be referred to a urologist who specializes in infertility to be evaluated for reversible causes of male factor infertility.
  11. 11. Table: Reference values for semen analysis Parameter Normal value Volume 2.0 ml or more PH 7.2-7.8 Sperm concentration 20 million/ml or more Motility 50% or more with progressive Motility (Grade a or b)∗ Morphology 15–30%† Viability 75% or more live White blood cells Fewer than million/ml ∗ Grade a: rapid progressive motility; Grade b: slow or sluggish motility.
  12. 12. B- Exclusion of Cervical Factor Infertility. The postcoital test (PCT) or Huhner's test allows direct analysis of sperm and cervical mucus interaction and provides a rough estimate of sperm quality. The test is done between days 12 and 14 of a 28- to 30-day menstrual cycle (after 48 hours of abstinence) when maximum estrogen secretion is present. The mucus is examined within 2 to 8 hours. Because interpretation of the PCT is subjective, the validity of the test is controversial, despite its long history of use. However, a finding of 5 to 10 progressively motile spermatozoa per high-power field and clear acellular mucus with a spinnbarkeit (the degree to which the mucus stretches between two slides) of 6-8 cm generally excludes a cervical factor.
  13. 13. The most common cause of an abnormal PCT is poor timing. Other causes include cervical stenosis, hypoplastic endocervical canal, coital dysfunction, and male factors. The sample can also be assessed for pH, mucus cellularity, WBC, and ferning. Clumping and flagellation of sperm without progression are often suggestive of antisperm antibodies.
  14. 14. C- Exclusion of Ovulatory Factor Infertility To exclude ovulatory dysfunction, the presence of ovulation must be confirmed. In addition, ovarian reserve should be assessed to exclude oocyte depletion or aging, and premature ovarian failure
  15. 15. Confirmation of Ovulation 1-The basal body temperature (BBT) chart is a simple means of determining whether ovulation has occurred. The woman's temperature is taken daily with a thermometer on awakening, before any activity, and is recorded on a graph. After ovulation, rising progesterone levels increase the basal temperature by approximately 0.4c° through a hypothalamic thermogenic effect. Because the rise in progesterone may occur anytime from 2 days before ovulation to 1 day after, the temperature elevation does not predict the exact moment of ovulation but offers retrospective confirmation of its occurrence. A temperature elevation that persists for less than 11 days is suggestive but not diagnostic of a luteal phase defect.
  16. 16. 2-Midluteal phase progesterone level is another test to assess ovulation. A concentration greater than 3.0 ng/mL in a blood sample drawn between days 19 and 23 is consistent with ovulation, whereas a concentration greater than 10 ng/mL implies adequate luteal support. 3-Daily monitoring of urinary LH has been widely available given the proliferation of commercial tests for home use. Using a threshold concentration of 40 mIU/mL, positive testing for urinary LH has been shown to correlate well with the surge of serum LH levels that trigger ovulation.
  17. 17. Assessment of Ovarian Reserve Depleted ovarian reserve adversely impacts fecundability given the inferior quantity and quality of remaining oocytes. The following tests help identify both a depleted reserve and the likelihood of response to controlled ovarian hyperstimulation during assisted reproduction: Day 3 FSH concentration: Values under 10 to 15 mIU/mL suggest adequate ovarian reserve. The exact cutoff depends on the particular laboratory reference standards.
  18. 18. Clomiphene citrate challenge test (CCCT): The administration of clomiphene citrate 100 mg orally on menstrual cycle days 5 to 9 with measurement of Day 3 and Day 10 FSH. An exaggerated FSH response portends poorly for spontaneous or assisted conception. Imaging of antral follicle counts by ultrasonography.
  19. 19. D- Exclusion of Structural Factors (tubal blockage) The hysterosalpingogram (HSG) assesses uterine and fallopian tube contour and tubal patency and is performed in the early follicular phase, within 1 week of cessation of menstrual flow. This timing minimizes the chances of interrupting a pregnancy. The procedure is performed by injecting a radiopaque dye through the cervix.
  20. 20. As more dye is injected, the dye passes through the uterine cavity into the fallopian tubes and peritoneal cavity. X-ray films are taken under fluoroscopy to demonstrate patent or obstructed tubes. Nonsteroidal anti-inflammatory drugs may be given to prevent cramping. Prophylactic antibiotics (e.g., doxycycline, 100 mg orally twice daily) are advisable when the patient has a history of pelvic inflammatory disease or when hydrosalpinges are identified during the study
  21. 21. A diagnostic laparoscopy assesses peritoneal and tubal factors, such as endometriosis and pelvic adhesions, and can provide access for simultaneous corrective surgery. Laparoscopy should be scheduled in the follicular phase and is the final and most invasive step in the patient's evaluation, unless the HSG raised suspicion of abnormalities. Findings on HSG correlate with laparoscopic findings 60% to 70% of the time.
  22. 22. Dye (usually a dilute solution of indigo carmine) should be instilled through the fallopian tubes (chromopertubation) during laparoscopy to visually document tubal patency. Hysteroscopy may also be included to ensure that no intrauterine abnormalities were missed on the HSG. Recently, however, questions have been raised regarding the propriety and usefulness of pursuing laparoscopy following a normal HSG.
  23. 23. . Treatment 1-Anovulation. The WHO stratifies anovulatory women into three classes: WHO Class I: Hypogonadotropic hypogonadal anovulation encompasses hypothalamic amenorrhea attributable to low GnRH levels or pituitary unresponsiveness to hypothalamic GnRH, with resultant low FSH and serum estradiol levels. WHO Class II: Normogonadotropic normoestrogenic anovulation involves normal levels of estradiol and FSH; LH levels, however, are elevated. This class includes the polycystic ovarian syndrome (PCOS). WHO Class III: Hypergonadotropic hypoestrogenic anovulation results from premature ovarian failure or ovarian resistance.
  24. 24. The vast majority of anovulatory women of reproductive age fall into WHO class II and, fortunately, this class proves responsive to ovulation induction. The agents most commonly used to stimulate multiple ovarian follicles are  clomiphene citrate (CC), human menopausal gonadotropins (hMG),  purified follicle-stimulating hormone (FSH). CC, a synthetic, nonsteroidal estrogen agonist-antagonist, increases the release of gonadotropin-releasing hormone (GnRH) and subsequent LH and FSH release.
  25. 25. CC is useful in women with oligomenorrhea and amenorrhea, with intact hypothalamic-pituitary-ovarian axes. Patients who are overweight and hyperandrogenic have decreased responsiveness to CC. Women with PCOS often respond to metformin administered with or in lieu of CC. GnRH, hMG, and FSH are used primarily in women who fail to respond to CC or who have hypogonadotropic amenorrhea or unexplained infertility. Prescription of these expensive drugs, which are used in the more complicated protocols for in vitro fertilization , should be left to specialists trained in their use
  26. 26. 2-Hyperprolactinemia. to induce ovulation in patients with hyperprolactinemia the use of the dopamine agonists bromocriptine (Parlodel) or carbergoline (Dostinex ) is the best way. Bromocriptine is a dopamine agonist that directly inhibits pituitary secretion of prolactin, which restores normal gonadotropin release. The usual starting dose is 2.5 mg at bedtime to prevent dopaminergic side effects, which include nausea, diarrhea, dizziness, and headache. If oral administration cannot be tolerated, vaginal administration is recommended. A response is usually seen in 2 to 3 months, and 80% of hyperprolactinemic patients ovulate and become pregnant. CC is added if ovulation does not occur within 3 months after beginning treatment.
  27. 27. 3-Other, Thyroid problems should be treated appropriately because both hypothyroidism and hyperthyroidism may lead to infertility. Hypothalamic-pituitary axis problems, including extreme weight gain or loss, excessive exercise, and emotional stress, can all impact the secretion of GnRH from the hypothalamus and cause ovulatory dysfunction. These must be addressed by appropriate behavioral or psychological intervention.
  28. 28. 4-Male Factor Infertility. Although the gynecologist does not directly treat male patients, therapies to treat male factor infertility often involve hormonal manipulation in the female partner. The evaluation is analogous to that in the woman, with examination of the hypothalamic-pituitary-testicular axis, outflow tract, and testicular function. Toxins, viruses, sexually transmitted diseases, varicoceles, and congenital problems can all influence infertility.. At present, these abnormalities of volume are most commonly treated with sperm washing and intrauterine insemination (IUI).
  29. 29. The initiation of intracytoplasmic sperm injection (ICSI) has revolutionized treatment of male infertility. As long as viable sperm can be retrieved by ejaculation, epididymal aspiration, or testicular biopsy, successful fertilization and pregnancy can be achieved. The fertilization rate is 95%, and the pregnancy rate is comparable to that of in vitro fertilization (IVF).
  30. 30. 3- Endometriosis, the ectopic growth of hormonally responsive endometrial tissue, may account for 15% of infertility in women; endometriosis is diagnosed and staged by laparoscopy, it has a negative impact on fertility, and, once diagnosed, it should be treated surgically before instituting infertility therapy. Laparoscopic resection or ablation of even minimal endometriosis may enhance fecundity in infertile women.
  31. 31. If pregnancy fails to occur after surgical treatment, the patient should be directed to an infertility specialist for possible IVF. GnRH agonists, danazol, and continuous oral contraceptive pills effectively treat endometriosis-related pelvic pain, but they all prevent pregnancy
  32. 32. 4-Luteal phase defects occur in both fertile and infertile women, and treatment is highly controversial. Nevertheless, in a couple with documented infertility, care should be taken to treat a presumed luteal phase deficiency with intramuscular or intravaginal progesterone in the postovulatory phase of the cycle and if pregnancy occurs until the luteoplacental shift occurs
  33. 33. 5-Uterine factors, such as submucous leiomyomas, intrauterine synechia (Asherman's syndrome), and uterine deformities or septa, cause approximately 2% of infertility. The mainstay of treatment for these conditions is surgical correction, usually via a hysteroscopic approach. 6-Infections of the female and male genital tracts have been implicated as causes of infertility. Chlamydia infection and gonorrhea are the major pathogens and should be treated appropriately.
  34. 34. Ureaplasma urealyticum and Mycoplasma hominis have also been implicated, and, if positively identified by culture, they should be treated with oral doxycycline, 100 mg twice daily for 7 days. This has been shown to increase the pregnancy rate in patients with primary infertility.
  35. 35. 6-Tubal factor infertility has become more prevalent with the increased incidence of salpingitis. The frequency of tubal occlusion after one, two, and three episodes of salpingitis is reported to be 11%, 23%, and 54%, respectively. Appendicitis, previous abdominopelvic surgery, endometriosis, and ectopic pregnancy can also lead to adhesion formation and damaged tubes. Proximal tubal obstruction is identified on HSG.
  36. 36. Tubal spasm may mimic proximal obstruction, however, and obstruction should be confirmed by laparoscopy. Treatment consists of tubal cannulation, microsurgical tubocornual reanastomosis, or IVF. Distal tubal disease or distortion can be seen on HSG and laparoscopy. The success of corrective surgery (neosalpingostomy) depends on the extent of disease.
  37. 37. Assisted Reproduction Technology 38
  38. 38. Definition of ART • ART refers to all techniques involving direct retrieval of oocytes from the ovary • ART procedures include IVF, GIFT, ZIFT, and ICSI. • The simplest ART procedure, IVF has been around for over 20 years and is perhaps the most commonly recognized ART of all procedures. Abdulkareem Sultan Al-Olama 39
  39. 39. Abbreviations used in assisted conception • IVF In-vitro fertilization • DI Donor insemination • GIFT Gamete intrafaillopian transfer • ZIFT Zygote intrafallopian transfer • SUZI Subzonal insemination • ICSI Intracytoplasmic sperm injection • PESA Percutaneous sperm aspiration • MESA Micro-epididymal sperm aspiration • TESA Testicular sperm aspiration
  40. 40. Controlled Ovarian Hyperstimulation (COH) and Protocols for In Vitro Fertilization. The agents most commonly used to stimulate multiple ovarian follicles are CC, hMG, and purified FSH.
  41. 41. 1-Clomiphene-only regimens are generally given on days 5 to 9 of the menstrual cycle. Response may be followed by BBT measurement, ultrasonography, and measurement of LH and estradiol levels. CC is inexpensive and 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 50 mg per day for 5 days. If ovulation fails to occur, the dose is increased to 100 mg per day. Human chorionic gonadotropin (hCG), 5,000 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 are vasomotor flushes, blurring of vision, urticaria, pain, bloating, and multiple gestation (5% to 7% of cases, usually twins).
  42. 42. 2-Gonadotropin regimens increase the number of recruited follicles in patients who do not achieve pregnancy with CC and in those patients with endometriosis or unexplained infertility. The hMG, which is a combination of LH and FSH, is usually given for 2 to 7 days. Although gonadotropin injections prove more effective at COH than clomiphene, they are more expensive and can lead to life-threatening OHSS. Trade names for hMG include Humegon, Pergonal, and Repronex. Attempts to minimize the potentially deleterious LH component of hMG have led to the manufacture of purified urinary FSH and, more recently, recombinant FSH.. Follicle maturation during COH is monitored using sonography and serial measurement of estradiol levels.
  43. 43. To complete oocyte maturation, hCG is administered once the follicles have reached 17 to 18 mm in diameter. Potential disadvantages of gonadotropin use include premature luteinization, spontaneous LH surges resulting in high cancellation rates, multiple gestations, and ovarian hyperstimulation.
  44. 44. 3-Gonadotropin-releasing hormone analogs/agonists (GnRHa) are used via a flare-up protocol or a luteal phase protocol. The 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. The luteal phase protocol involves starting GnRHa administration on the 17th to 21st menstrual day in the cycle before IVF. 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.
  45. 45. Oocyte Retrieval, Culture Fertilization, and Transfer The two major techniques of oocyte retrieval are 1-ultrasonographically guided follicular aspiration . The r is the most widely used technique. Ultrasonographically guided oocyte retrieval, using a 17-gauge needle passed through the vaginal fornix, is performed 34 to 36 hours after hCG injection. The procedure is done under heavy sedation. Potential complications include risk of bowel injury and injury to pelvic vessels. 2-laparoscopic oocyte retrieval
  46. 46. Oocyte Fertilization. Sperm are diluted, centrifuged, and incubated before 50,000 to 100,000 motile spermatozoa are added to each Petri dish containing an oocyte. Fertilization is documented by the presence of two pronuclei and extrusion of a second polar body at 24 hours. At that stage, most embryos are cryopreserved for an unlimited period, with a survival rate of 75%.
  47. 47. Embryo transfer is most commonly carried out 72 hours after retrieval at the 4- to 10-cell stage. In general, no more than two embryos are transferred to limit the risk of multiple gestation and to optimize pregnancy rates. The actual number of embryos transferred depends on the individual's age and other risk factors for multiple pregnancy. The common practice is to supplement the luteal phase with progesterone given by vaginal suppository, beginning the day of oocyte release and continuing into the 12th week of pregnancy
  48. 48. . Maternal, Fetal, and Long-Term Effects of ART Ovarian Hyperstimulation Syndrome (OHSS). Although commonly self-limited, the OHSS can present as a life-threatening complication of COH characterized by abdominal bloating, accumulation of ascites, decreased urine output, hemoconcentration, hypercoagulability, hydrothorax, ARDS, electrolyte imbalance, and multiple organ failure. Potentiated by COH cycles using GnRH analogs for down-regulation or hCG to trigger oocyte maturation, OHSS is classified as mild, moderate, or severe according to the presenting constellation of symptoms. Purported risk factors include young age, low body weight, high or rapidly climbing estradiol levels, large size and number of follicles, and the presence of PCOS.
  49. 49. Prevention of suspected impending OHSS can be achieved by lowering or withholding the hCG triggering dose, postponing embryo transfer, or canceling the cycle. Inpatient management for moderate-severe cases of OHSS includes close monitoring of fluid status and laboratory values of renal and coagulation function, intravascular resuscitation, thrombosis prophylaxis, paracentesis/thoracentesis as indicated, and critical care intervention if warranted. One must remember that OHSS is an entirely iatrogenic entity that is usually avoidable by vigilance and judicious execution and alteration of COH regimen.
  50. 50. . Preimplantation Genetic Diagnosis (PGD) •whereby parents could prevent the transmission of genetic disorders to their offspring and simultaneously avoid the emotional angst and ethical conundrum of pregnancy termination associated with conventional prenatal diagnosis. The process of PGD proceeds by biopsy and genetic analysis of one of the following specimens: •1 to 2 blastomeres of a cleavage-stage (Days 2 - 3) embryo derived from IVF •Polar body biopsy from a metaphase II oocyte obtained after COH •Trophectoderm tissue from a blastocyst-stage (Day 5) embryo
  51. 51. •PGD s used in the following •Single-Gene Disorders. PGD is used for multiple indications. Using the polymerase chain reaction (PCR), DNA extracted from the biopsy specimen is used to screen for a known hereditary disorder”for example, cystic fibrosis, muscular dystrophy, and Huntington's disease.
  52. 52. • Aneuploidy Testing. Fluorescence in situ hybridization (FISH) is a molecular technique predicated on the identification of chromosome-specific sequences that can be hybridized to complementary probes attached to differentially colored fluorochromes. •Sibling HLA-Matching. •PGD was first used in 2000 to screen for Fanconi anemia and simultaneously to select for a preimplantation embryo that was HLA-matched to a pre-existingElective Sex Selection. PGD, via either PCR or FISH, enables efficient and accurate gender selection by screening selectively for, or against, the Y chromosome. Sharp debate over the propriety of such nonmedical use of reproductive technology has limited the prevalence of this application.
  53. 53. Who is eligible for ART • Women with tubal diseases • Unexplained infertility • Endometriosis • Immunologic causes for infertility • Women with premature ovarian failure • Individuals with male factor infertility (e.g., abnormalities in sperm production, function or transport or prior vasectomy) Abdulkareem Sultan Al-Olama 54
  54. 54. Methodology of ovulation induction • The success of ovulation induction in achieving a pregnancy is highly variable. It depends on the diagnosis, age, the medication being used, and numerous other factors. Abdulkareem Sultan Al-Olama 55
  55. 55. Improving SPA • Sperm penetration assay (SPA) is a multi-step laboratory test that offers a biological assessment of human sperm fertilizing ability. Abdulkareem Sultan Al-Olama 56
  56. 56. Other techniques • ZIFT • GIFT • TEST • POST • ICSI • TESE • MESA Abdulkareem Sultan Al-Olama 57
  57. 57. Other techniques Cont’d • ZIFT – Zygote Intrafallopian Transfer. ZIFT may be recommended if the husband has severe male fertility factor or if there has been difficulty confirming fertilization with past procedures. ZIFT has the advantages of allowing fertilization to be confirmed and it has demonstrated higher success rates than IVF when used for the appropriate indications. – One disadvantage with ZIFT is that the transfer of the zygote must be performed through a laparoscope. 58
  58. 58. Other techniques Cont’d • GIFT – Gamete intrafallopian transfer was developing in 1984 as a variation of in vitro fertilization (IVF). – Gift is recommended when • unexplained infertility • infertility due to immunological factors • endometriosis • selected cases of male infertility • Tubal infertility – A requirement for the procedure is that the female partner having at least one open (patent) fallopian tube. 59
  59. 59. Other techniques Cont’d • TEST – Tubal Embryo Transfer; the placing of cleaving embryos into the fallopian tube. • POST – Peritoneal Oocyte and Sperm Transfer; the placement of oocytes and sperm into the pelvic cavity 60
  60. 60. Other techniques Cont’d • ICSI – Intracytoplasmic sperm injection, or ICSI, was developed to treat couples who previously had a very poor probability of achieving fertilization due to the male partner's extremely low numbers of viable sperm. – This treatment, when combined with in vitro fertilization, allows these couples a more favorable probability of achieving conception. 61
  61. 61. Other techniques Cont’d • TESE – Testicular Sperm Extraction • MESA – Microsurgical Epididymal Sperm Aspiration 62
  62. 62. Success rates "take home baby rate" • One of the first questions that most people ask is "what is the chance for success?" The best estimate is that the birth of a live baby occurs in approximately 15-25% of women in whom embryos are transferred into the uterus. • The 1998 nationwide live birth rate as reported in the IVF-ET Registry, was 24.9%. • The corresponding rate for 1989 was 14%. 63
  63. 63. Success rates Cont’d • Success varies with many factors, including the number of embryos that are transferred. • If one embryo is transferred, there is approximately a 7% chance of successful implantation; with two embryos, the success rate increases to 18%. • The rate peaks with the transfer of three to four embryos. Presently, the collection of oocytes, fertilization, and early embryo growth are accomplished with a high degree of efficiency. 64
  64. 64. Success rates Cont’d • The major hurdles to success are implantation after embryo transfer and early pregnancy loss. The rate of early pregnancy loss is slightly, but not significantly, higher with ART compared to spontaneous conception. • The risk of early pregnancy loss increases with age of the female partner. Over age 40, ART success rates decline dramatically. • Pregnancy complications tend to be higher with ART pregnancies, primarily because of the much higher rate of multiple pregnancy. 65
  65. 65. Success rates Cont’d • Twins occur in about 25% of ART pregnancies versus 1-2%of spontaneous pregnancies. The risk of more than a twin pregnancy is less than 5%. • To put these figures into perspective, studies have shown that the rate of pregnancy in couples with proven fertility in the past is approximately 20% per cycle. Therefore, although a figure of 15-25% may sound low, it is equal to or greater than the chance that a fertile couple will conceive in any given cycle. Abdulkareem Sultan Al-Olama 66
  66. 66. 67
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