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Nandaram Seervi
SMS MEDICAL COLLEGE JAIPUR
MANAGEMENT PROTOCOL FOR PRIMARY
AND SECONDARY INFERTILITY
Objectives
• Define primary and secondary infertility
• Describe the causes of infertility
• Diagnosis and management of infertility
Requirements for Conception
• Production of healthy egg and sperm
• Unblocked tubes that allow sperm to reach the egg
• The sperms ability to penetrate and fertilize the egg
• Implantation of the embryo into the uterus
• Finally a healthy pregnancy
Definition of Infertility
The inability to conceive following unprotected sexual
intercourse
• 1 year (age < 35) or 6 months (age >35)
• Affects 15% of reproductive couples
• Men and women equally affected
Type of Infertility
• Primary infertility
– a couple that has never conceived
• Secondary infertility
– infertility that occurs after previous pregnancy
regardless of outcome(abortion/actopic preg)
Causes for infertility
• Anovulation (10-20%)
• Anatomic defects of the female genital tract (30%)
• Abnormal spermatogenesis (40%)
• Unexplained (10%-20%)
Evaluation of the Infertile couple
• History and Physical exam
• Semen analysis
• Thyroid and prolactin evaluation
• Determination of ovulation
– Basal body temperature record
– Serum progesterone
– Ovarian reserve testing
• Hysterosalpingogram
Abnormalities of Spermatogenesis
Male Factor
• 40% of the cause for infertility
• Sperm is constantly produced by the germinal
epithelium of the testicle
– Sperm generation time 73 days
– Sperm production is thermoregulated
• 1° F less than body temperature
• Both men and women can produce anti-sperm
antibodies which interfere with the penetration of the
cervical mucus
Semen Analysis (SA)
• Obtained by masturbation
• Provides immediate information
– Quantity
– Quality
– Density of the sperm
• Abstain from coitus 2 to 3 days
• Collect all the ejaculate
• Analyze within 1 hour
• A normal semen analysis excludes male factor 90% of
the time
Normal Values for Semen Analysis(WHO-2010
normal & lower reference limit )
– Volume - 2.0 ml or more (1.5ml )
– pH - 7.2-7.8
– Viscosity - Liquefaction in 30-60 min
– Sperm Conc. - 20 million/ml or more (15mililion/ml )
– Total sperm count- >40 million/ejacu (39 million/ejacul )
– Viability - >75% living ( 58% )
– Motility - >50% forward progression (32% progressive
motility )
– Morphology – >14 % normal forms ( 4% )
– WBC - < 1 million/ml
– Round cells < 5 million/ml
Causes for male infertility
• 42% varicocele
– repair if there is a low count or decreased motility
• 22% idiopathic
• 14% obstruction
• 20% other (genetic abnormalities)
Evaluation of Ovulation
Menstruation
• Ovulation occurs 13-14 times per year
• Menstrual cycles on average are 28 days with ovulation
around day 14
• Luteal phase
– dominated by the secretion of progesterone
– released by the corpus luteum
• Progesterone causes
– Thickening of the endocervical mucus
– Increases the basal body temperature (0.6° F)
• Involution of the corpus luteum causes a fall in
progesterone and the onset of menses
Ovulation
• A history of regular menstruation suggests regular
ovulation
• The majority of ovulatory women experience
– fullness of the breasts
– decreased vaginal secretions
– abdominal bloating
• Absence of PMS symptoms may suggest anovulation
Diagnostic studies to confirm Ovulation
Basal Body Temperature
• Basal body temperature
– Inexpensive
– Accurate
• Endometrial biopsy
– Expensive
– Static information
• Serum progesterone
– After ovulation rises
– Can be measured
• Urinary ovulation-detection kits
– Measures changes in urinary LH
– Predicts ovulation but does not confirm it
Serum Progesterone
• Progesterone starts rising with the LH surge
– drawn between day 21-24
– Mid-luteal phase
– >10 ng/ml suggests ovulation
• Anovulation
Symptoms
• Irregular menstrual cycles
• Amenorrhea
• Hirsuitism
• Acne
• Galactorrhea
• Increased vaginal secretions
Evaluation*
• Follicle stimulating hormone
• Lutenizing hormone
• Thyroid stimulating hormone
• Prolactin
• Androstenedione
• Total testosterone
• DHEAS
Anatomic Disorders of the Female Genital Tract
Sperm transport, Fertilization, & Implantation
• The female genital tract is not just a conduit
– facilitates sperm transport
– cervical mucus traps the coagulated ejaculate
– the fallopian tube picks up the egg
• Fertilization must occur in the proximal portion of the
tube
– the fertilized oocyte cleaves and forms a zygote
– enters the endometrial cavity at 3 to 5 days
• Implants into the secretory endometrium for growth and
development
Acquired Disorders
• Acute salpingitis
– Alters the functional integrity of the fallopian tube
• N. gonorrhea and C. trachomatis
• Intrauterine scarring
– Can be caused by curettage
• Endometriosis, scarring from surgery, tumors of the
uterus and ovary
– Fibroids, endometriomas
Trauma
Congenital Anatomic Abnormalities
Hysterosalpingogram
•An X-ray that evaluates the internal female genital tract
– architecture and integrity of the system
•Performed between the 7th
and 11th
day of the cycle
•Diagnostic accuracy of 70%
•
• The endometrial cavity
– Smooth
– Symmetrical
• Fallopian tubes
– Proximal 2/3 slender
– Ampulla is dilated
• Dye should spill promptly
Unexplained infertility
• 10% of infertile couples will have a completely normal
workup
• Pregnancy rates in unexplained infertility
– no treatment 1.3-4.1%
– clomiphene and intrauterine insemination 8.3%
– gonadotropins and intrauterine insemination 17.1%
Treatment of the Infertile Couple
Inadequate Spermatogenesis
• Eliminate alterations of thermoregulation
• Clomiphene citrate is occasionally used for induction of
spermatogenesis
– 20% success
• In vitro fertilization may facilitate fertilization
• Artificial insemination with donor sperm is often
successful
Anovulation
• Restore ovulation
– Administer ovulation inducing agents
• Clomiphene citrate
– Antiestrogen
– Combines and blocks estrogen receptors at the
hypothalamus and pituitary causing a negative feedback
– Increases FSH production
• stimulates the ovary to make follicles
Clomiphene Citrate
• Given for 5 days in the early part of the cycle
• Maximum dose is usually 150mg
• 50mg dose - 50% ovulate
• 100mg -25% more ovulate
• 150mg lower numbers of ovulation
• No changes in birth defects If no pregnancy in 6 months
refer for advanced therapies
• 7% risk of twins 0.3% triplets
• SAB rate 15%
Superovulatory Medications
• If no response with clomiphane then gonadotropins- FSH
(e.g. pergonal) can be administered intramuscularly
– This is usually given under the guidance of someone who
specializes in infertility
• This therapy is expensive and patients need to be
followed closely
• Adverse effects
– Hyperstimulation of the ovaries
– Multiple gestation
– Fetal wastage
Anatomic Abnormalities
• Surgical treatments
– Lysis of adhesions
– Septoplasty
– Tuboplasty
– Myomectomy
• Surgery may be performed
– laparoscopically
– hysteroscopically
• If the fallopian tubes are beyond repair one must
consider in vitro fertilization
Assisted Reproductive Technologies (ART)
Intrauterine Insemination
Indications
Unexplained
Mild male factor
Success/Cycle---Natural 10-15%, Stimulated 15-20%
Question on management protocol of pri. & sec. infertility
1. Best prognosis in infertile women is seen in/most reversible form of infertility is :
(a) Tubal block
(b) Anovulation
(c) Oligospermia
(d) Endometritis
2. The risk of Asherman syndrome is the highest if Dilatation and Curettage (D&C) is done for the following
condition :
(a) Medical termination of pregnancy
(b) Missed abortion
(c) Dysfunctional uterine bleeding
(d) Post partum haemorrhage
3. Fern test is due to :
(a) Presence of NaCl under progesterone effect
(b) Presence of NaCl under estrogenic effect
(c) LH/FSH
(d) Mucus secretion by Glands
4. An infertile women has bilateral tubal block at cornua diagnosed on hysterosalpingography. Next step in
treatment is :
(a) IVF
(b) Laparoscopy and hysteroscopy
(c) Tuboplasty
(d) Hydrotubation
5. Post coital test detects all of the following except :
(a) Fallopian tube block
(b) Cervical factor abnormality
(c) Sperm count
(d) Sperm abnormality
6. A 25 year old infertile male underwent semen analysis. Results show : sperm count-15 million/ml; pH-
7.5; volume-2 ml; no agglutination is seen. Morphology shows 60% normal and 60% motile sperms. Most
likely diagnosis is :
(a) Normospermia
(b) Oligospermia
(c) Azoospermia
(d) Aspermia
7. Which of the following is true about obstructive azoospermia :
(a) FSH and LH
(b) Normal FSH and Normal LH
(c) LH, Normal FSH
(d) FSH, Normal LH
8. In azoospermia, the diagnostic test which can distinguish between testicular failure and obstruction of
Vas deferens is :
(a) Estimation of FSH level
(b) Estimation of testosterone level
(c) Karyotyping
(d) FNAC of testes
9. Semen analysis of a male of an infertile couple, shows absence of spermatozoa but presence of fructose.
The most probable diagnosis is :
(a) Prostatic infection
(b) Mumps orchitis
(c) Block in efferect duct system
(d) All of the above
10. Artificial insemination with husband’s semen is indicated in all the following situations, except :
(a) Oligospermia
(b) Impotency
(c) Antisperm antibodies in the cervical mucous
(d) Azoospermia
11. Aspiration of sperms from testes is done in :
(a) TESA
(b) MESA
(c) ZIFT
(d) GIFT
12. Luteal phse is best diagnosed by :
(a) Serum progesterone levels
(b) Endometrial biopsy
(c) Basal body temperature
(d) Ultrasonography
13. What is the optimal time during the menstrual cycle when serum progesterone should be drawn to
confirm the diagnosis of luteal phase deficiency :
(a) Day 18
(b) Day 21
(c) Day 23
(d) Day 25
14. All are used in treatment of infertility, except :
(a) Luteinizng hormone (LH)
(b) Prolactin
(c) GnRH
(d) Clomiphene
15. Asthenospermia means :
(a) Failure of the formation of sperms
(b) No spermatozoa in the semen
(c) Reduction in the motility of sperms
(d) Sperm count less than 20 million/ml of semen
Answers key
1.B
2.D
3.B
4.B
5.A
6.B
7.B
8. A
9. C
10. D
11. A
12. B
13. B
14. B
15. C
Pri. and secondary infertility

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Pri. and secondary infertility

  • 1. Nandaram Seervi SMS MEDICAL COLLEGE JAIPUR MANAGEMENT PROTOCOL FOR PRIMARY AND SECONDARY INFERTILITY Objectives • Define primary and secondary infertility • Describe the causes of infertility • Diagnosis and management of infertility Requirements for Conception • Production of healthy egg and sperm
  • 2. • Unblocked tubes that allow sperm to reach the egg • The sperms ability to penetrate and fertilize the egg • Implantation of the embryo into the uterus • Finally a healthy pregnancy Definition of Infertility The inability to conceive following unprotected sexual intercourse • 1 year (age < 35) or 6 months (age >35) • Affects 15% of reproductive couples • Men and women equally affected Type of Infertility • Primary infertility
  • 3. – a couple that has never conceived • Secondary infertility – infertility that occurs after previous pregnancy regardless of outcome(abortion/actopic preg) Causes for infertility • Anovulation (10-20%) • Anatomic defects of the female genital tract (30%) • Abnormal spermatogenesis (40%) • Unexplained (10%-20%) Evaluation of the Infertile couple • History and Physical exam • Semen analysis
  • 4. • Thyroid and prolactin evaluation • Determination of ovulation – Basal body temperature record – Serum progesterone – Ovarian reserve testing • Hysterosalpingogram Abnormalities of Spermatogenesis Male Factor • 40% of the cause for infertility • Sperm is constantly produced by the germinal epithelium of the testicle – Sperm generation time 73 days
  • 5. – Sperm production is thermoregulated • 1° F less than body temperature • Both men and women can produce anti-sperm antibodies which interfere with the penetration of the cervical mucus Semen Analysis (SA) • Obtained by masturbation • Provides immediate information – Quantity – Quality – Density of the sperm
  • 6. • Abstain from coitus 2 to 3 days • Collect all the ejaculate • Analyze within 1 hour • A normal semen analysis excludes male factor 90% of the time Normal Values for Semen Analysis(WHO-2010 normal & lower reference limit ) – Volume - 2.0 ml or more (1.5ml ) – pH - 7.2-7.8 – Viscosity - Liquefaction in 30-60 min – Sperm Conc. - 20 million/ml or more (15mililion/ml )
  • 7. – Total sperm count- >40 million/ejacu (39 million/ejacul ) – Viability - >75% living ( 58% ) – Motility - >50% forward progression (32% progressive motility ) – Morphology – >14 % normal forms ( 4% ) – WBC - < 1 million/ml – Round cells < 5 million/ml Causes for male infertility • 42% varicocele – repair if there is a low count or decreased motility • 22% idiopathic • 14% obstruction
  • 8. • 20% other (genetic abnormalities) Evaluation of Ovulation Menstruation • Ovulation occurs 13-14 times per year • Menstrual cycles on average are 28 days with ovulation around day 14 • Luteal phase – dominated by the secretion of progesterone – released by the corpus luteum • Progesterone causes – Thickening of the endocervical mucus
  • 9. – Increases the basal body temperature (0.6° F) • Involution of the corpus luteum causes a fall in progesterone and the onset of menses Ovulation • A history of regular menstruation suggests regular ovulation
  • 10. • The majority of ovulatory women experience – fullness of the breasts – decreased vaginal secretions – abdominal bloating • Absence of PMS symptoms may suggest anovulation Diagnostic studies to confirm Ovulation Basal Body Temperature • Basal body temperature – Inexpensive – Accurate • Endometrial biopsy
  • 11. – Expensive – Static information • Serum progesterone – After ovulation rises – Can be measured • Urinary ovulation-detection kits – Measures changes in urinary LH – Predicts ovulation but does not confirm it
  • 12. Serum Progesterone • Progesterone starts rising with the LH surge – drawn between day 21-24 – Mid-luteal phase – >10 ng/ml suggests ovulation
  • 13. • Anovulation Symptoms • Irregular menstrual cycles • Amenorrhea • Hirsuitism • Acne • Galactorrhea • Increased vaginal secretions
  • 14. Evaluation* • Follicle stimulating hormone • Lutenizing hormone • Thyroid stimulating hormone • Prolactin • Androstenedione • Total testosterone • DHEAS
  • 15. Anatomic Disorders of the Female Genital Tract Sperm transport, Fertilization, & Implantation • The female genital tract is not just a conduit – facilitates sperm transport – cervical mucus traps the coagulated ejaculate – the fallopian tube picks up the egg • Fertilization must occur in the proximal portion of the tube – the fertilized oocyte cleaves and forms a zygote – enters the endometrial cavity at 3 to 5 days • Implants into the secretory endometrium for growth and development
  • 16. Acquired Disorders • Acute salpingitis – Alters the functional integrity of the fallopian tube • N. gonorrhea and C. trachomatis • Intrauterine scarring – Can be caused by curettage • Endometriosis, scarring from surgery, tumors of the uterus and ovary – Fibroids, endometriomas Trauma Congenital Anatomic Abnormalities
  • 17. Hysterosalpingogram •An X-ray that evaluates the internal female genital tract – architecture and integrity of the system •Performed between the 7th and 11th day of the cycle •Diagnostic accuracy of 70% •
  • 18. • The endometrial cavity – Smooth – Symmetrical • Fallopian tubes – Proximal 2/3 slender – Ampulla is dilated • Dye should spill promptly
  • 19. Unexplained infertility • 10% of infertile couples will have a completely normal workup • Pregnancy rates in unexplained infertility – no treatment 1.3-4.1% – clomiphene and intrauterine insemination 8.3% – gonadotropins and intrauterine insemination 17.1% Treatment of the Infertile Couple Inadequate Spermatogenesis • Eliminate alterations of thermoregulation
  • 20. • Clomiphene citrate is occasionally used for induction of spermatogenesis – 20% success • In vitro fertilization may facilitate fertilization • Artificial insemination with donor sperm is often successful Anovulation • Restore ovulation – Administer ovulation inducing agents • Clomiphene citrate – Antiestrogen
  • 21. – Combines and blocks estrogen receptors at the hypothalamus and pituitary causing a negative feedback – Increases FSH production • stimulates the ovary to make follicles Clomiphene Citrate • Given for 5 days in the early part of the cycle • Maximum dose is usually 150mg • 50mg dose - 50% ovulate • 100mg -25% more ovulate • 150mg lower numbers of ovulation • No changes in birth defects If no pregnancy in 6 months refer for advanced therapies
  • 22. • 7% risk of twins 0.3% triplets • SAB rate 15% Superovulatory Medications • If no response with clomiphane then gonadotropins- FSH (e.g. pergonal) can be administered intramuscularly – This is usually given under the guidance of someone who specializes in infertility • This therapy is expensive and patients need to be followed closely • Adverse effects – Hyperstimulation of the ovaries – Multiple gestation
  • 23. – Fetal wastage Anatomic Abnormalities • Surgical treatments – Lysis of adhesions – Septoplasty – Tuboplasty – Myomectomy • Surgery may be performed – laparoscopically – hysteroscopically • If the fallopian tubes are beyond repair one must consider in vitro fertilization
  • 24. Assisted Reproductive Technologies (ART) Intrauterine Insemination Indications Unexplained Mild male factor Success/Cycle---Natural 10-15%, Stimulated 15-20% Question on management protocol of pri. & sec. infertility 1. Best prognosis in infertile women is seen in/most reversible form of infertility is : (a) Tubal block (b) Anovulation (c) Oligospermia (d) Endometritis
  • 25. 2. The risk of Asherman syndrome is the highest if Dilatation and Curettage (D&C) is done for the following condition : (a) Medical termination of pregnancy (b) Missed abortion (c) Dysfunctional uterine bleeding (d) Post partum haemorrhage 3. Fern test is due to : (a) Presence of NaCl under progesterone effect (b) Presence of NaCl under estrogenic effect (c) LH/FSH (d) Mucus secretion by Glands 4. An infertile women has bilateral tubal block at cornua diagnosed on hysterosalpingography. Next step in treatment is : (a) IVF (b) Laparoscopy and hysteroscopy (c) Tuboplasty (d) Hydrotubation 5. Post coital test detects all of the following except : (a) Fallopian tube block (b) Cervical factor abnormality (c) Sperm count (d) Sperm abnormality 6. A 25 year old infertile male underwent semen analysis. Results show : sperm count-15 million/ml; pH- 7.5; volume-2 ml; no agglutination is seen. Morphology shows 60% normal and 60% motile sperms. Most likely diagnosis is : (a) Normospermia (b) Oligospermia
  • 26. (c) Azoospermia (d) Aspermia 7. Which of the following is true about obstructive azoospermia : (a) FSH and LH (b) Normal FSH and Normal LH (c) LH, Normal FSH (d) FSH, Normal LH 8. In azoospermia, the diagnostic test which can distinguish between testicular failure and obstruction of Vas deferens is : (a) Estimation of FSH level (b) Estimation of testosterone level (c) Karyotyping (d) FNAC of testes 9. Semen analysis of a male of an infertile couple, shows absence of spermatozoa but presence of fructose. The most probable diagnosis is : (a) Prostatic infection (b) Mumps orchitis (c) Block in efferect duct system (d) All of the above 10. Artificial insemination with husband’s semen is indicated in all the following situations, except : (a) Oligospermia (b) Impotency (c) Antisperm antibodies in the cervical mucous (d) Azoospermia 11. Aspiration of sperms from testes is done in : (a) TESA
  • 27. (b) MESA (c) ZIFT (d) GIFT 12. Luteal phse is best diagnosed by : (a) Serum progesterone levels (b) Endometrial biopsy (c) Basal body temperature (d) Ultrasonography 13. What is the optimal time during the menstrual cycle when serum progesterone should be drawn to confirm the diagnosis of luteal phase deficiency : (a) Day 18 (b) Day 21 (c) Day 23 (d) Day 25 14. All are used in treatment of infertility, except : (a) Luteinizng hormone (LH) (b) Prolactin (c) GnRH (d) Clomiphene 15. Asthenospermia means : (a) Failure of the formation of sperms (b) No spermatozoa in the semen (c) Reduction in the motility of sperms (d) Sperm count less than 20 million/ml of semen
  • 28. Answers key 1.B 2.D 3.B 4.B 5.A 6.B 7.B 8. A 9. C 10. D 11. A 12. B 13. B 14. B 15. C