2. WHEN TO EVALUATE:
• All couples who fail to conceive after a year or more of regular unprotected
intercourse.
• Earlier evaluation is needed in : Age > 35 years
Irregular menses
Pelvic infection
Endometriosis
Known male factors
3. FACTORS AFFECTING MANAGEMENT OF INFERTILITY
• Age of both the partners
• Duration of infertility
• Prior treatment failure
• Cause of infertility
4. COUNSELLING
• Male and Female partner are evaluated together
• Proper & accurate information is provided to the couple about :
1)The act and timing of coitus
2)Nature of therapy
3)Cost of therapy
4)Treatment options available
• Its important to mention to the couple that the probability of
unexplained infertility is 10-15%.
• Couple is motivated not to change consultants regularly & be compliant
to therapy. Positive attitude is needed.
10. DECREASED OVARIAN RESERVE:
• There is a decrease in fecundability as the age advances which is physiological
• Size and quality of remaining follicular pool.
• 10 to 15 yrs before menopause, there is an acceleration of follicular loss
• By the age of 37 to 38yrs, no. of follicles reaches upto 25,000.
• This loss correlates to increase in FSH level and decrease in inhibin B
• These changes reflects reduced quality and capability of aging follicles
11. DAY 3 FSH > 12 TO 20 IU/ml
DAY 3 ESTRADIOL > 80 pg/ml
• Associated with poor performance for OI / ART and predictors of difficulty in
achieving pregnancy
• Treatment options for decreased ovarian reserve include IVF(use of donor
oocytes) and adoption
12. OVULATION INDUCTION
GOAL: Therapeutic restoration of the release of one egg per cycle in a
women who either has not been ovulating regularly or has not been
ovulating at all
DRUGS USED IN OVULATION INDUCTION
• Clomiphene citrate
• Aromatase inhibitors
• Exogenous Gonadotropins
13. CLOMIPHENE CITRATE
• Non steroidal triphenylethylene derivative
• Selective Estrogen Receptor Modulator (SERM)
• Purely Anti estrogen/antagonist
• Weak estrogenic action apparent only when endogenous estrogen is very low
• Racemic mixture
• Enclomiphene –more potent. Half life – short,rise & fall quickly during & after
treatment.
• Zuclomiphene- Cleared much slowly.serum levels detectable after weeks.
Cis isomer -Enclomiphene( 62%).
Trans isomer -Zuclomiphene( 38%).
14. MECHANISM OF ACTION
Depletion of hypothalamic ER prevents
correct interpretation of circulating
estrogen levels, falsely perceived as low
(-) feedback alter pattern of GnRH
secretion pituitary gonadotropins
ovarian follicular development
At pituitary level, CC increase sensitivity of
gonadotrophs to GnRH stimulation
CC binds to nuclear estrogen receptors&
deplets it by interfering with receptor
recycling
15. INDICATIONS
• Anovulation –TOC of most anovulatory or oligo- ovulatory infertile women
who are euthyroid, euprolactinemic & with normal circulating estrogen levels.
• Luteal phase deficiency –Progesterone levels higher after CC treatment than in
spontaneous cycles( improved preovulatory follicles, corpus luteal
development, hormone from more than one CL)
• Unexplained infertility – correction of subtle / unrecognised ovulatory
dysfunction /Superovulation of more than a single ovum.More effective if
combined with properly timed IUI.
17. STAIR STEP REGIMEN- To shorten the time required for ovulation
Day 5 -9 ( CC -50mg )
Day 11-14 (USG - <15mmDF)
Day 11-14 (CC-100mg)
Day21 (USG- <15mmDF)
Day21 ( CC-150mg)
Day 27 ( USG )
18. SIDE EFFECTS:
• It exerts undesirable adverse antiestrogenic effects on the periphery
(endocervix and endometrium)
• Transient hot flushes
• Mood swings
• Head ache, breast tenderness, pelvic pressure/pain and nausea
• Visual disturbances and light sensitivity
19. RISKS AND COMPLICATIONS:
MULTIPLE GESTATION:
• Multi follicular development with clomiphene is relatively common and
overall risk is increased to 7-10%
• Higher doses of clomiphene has risk of superovulation and multiple pregnancy
OHSS:
• Mild variety of ovarian hyper stimulation syndrome is relatively common ,
severe OHSS is rarely observed
• No relationship between OI drugs and ovarian/breast cancer has been
observed till date
20. RESULTS WITH CC:
• Successful ovulation is seen in 70-80% of properly selected women
• When there is no ovulation seen with 3 cycles of clomiphene, it is
considered clomiphene resistance
• When pregnancy is not achieved in 3-6 clomiphene induced ovulatory
cycles, it is considered as clomiphene failure
• Infertility evaluation is further expanded in such cases to rule out other
causes
ADJUVANT AND COMBINATION TREATMENTS :
a)CC+ Glucocorticids
b)CC+hCG
c)CC+ Metformin
d)Preliminary suppressive therapy with OCP’s
21. CC and Glucocorticoids:
• Androgen suppression , direct effects on developing oocyte , indirect
effects on intrafollicular growth factors & cytokines – acts synergistically
with FSH.
• Prednisolone 5mg or dexamethasone 0.5-2mg daily ( D5-14)
CC and hCG:
• Exogenous hCG – surrogate LH surge to trigger ovulation in clomiphene
induced cycles esp when IUI is done.
• Given when preovulatory follicle is 18- 20 mm in dm.
• Ovulation occurs 34-46 hrs after hCG injection, so IUI done 36 hrs later.
22. CC and Metformin:
• Insulin resistance & hyperinsulinemia – PCOS
• Metformin – a biguanide ,Oral insulin sensitizing agent
• hepatic gluconeogenesis , peripheral utilisation of glucose, intestinal
absorption of glucose
• Considered before proceeding to ovarian drilling or gonadotropin therapy
in clomiphene resistant patients
Preliminary suppressive therapy :
• In a previous clomiphene resistant women,2 month interval of continuous
OCP supresses Sr.LH & androgen levels , ovulation occurs in 70% with CC
.
• GnRH agonist alone or with OCP
23. AROMATASE INHIBITORS
• Letrozole & Anastrozole – triazole ( antifungal) derivatives – Potent ,
Competitive inhibitors of aromatase- the enzyme catalysing rate limiting
step in estrogen productin.
• Blocks estrogen production both in periphery & brain--> gonadotropin
secretion ovarian follicular development
REGIMEN:
Letrozole 2.5-5mg daily
Anastrozole 1mg daily X 5 Days
24.
25. CLOMIPHENE CITRATE LETROZOLE
Acts by depletion of central estrogen receptors Decreases estrogen production directly
After the treatment ends, rising estrogen level cannot exert
negative feedback immediately.
After treatment ends, rising estrogen from growing follicles exert
negative feedback immediately.
More sustained increase in gonadotropin levels promotes
multifollicular development
Promotes development of single dominant follicle.
Inhibits endometrial proliferation & cervical mucus
production
Do not interfere with actions of estrogen in the periphery
26. EXOGENOUS GONADOTROPINS
1)Human menopausal gonadotropin ( hMG, menotropin)- from urine of
postmenopausal women
• Contains 75IU of FSH and LH per ampule
• Route:IM
2)Purified urinary FSH ( urofollitropin)
3)Recombinant FSH – follitropin alpha & beta( functionally same but post translational
glycosylation process & purification procedures different )
4)Recombinant LH
5)Recombinant hCG- Structurally & biologically similar to LH.
Stimulates LH surge & induce ovulation in gonadotropin stimulated cycles.
Promotes final stages of follicular & oocyte maturation ( prophase I, germinal vesical
stage , meiosis , metaphase II) requires 36 hours to complete & ovulation occurs 4
hours later.
28. • Hypogonadotropic hypogonadism :
• Women with hypothalamic amenorrhoea ( WHO-Group 1)
• Hormone therapy intended to stimulate normal cyclic ovulation.
• DOC: Menotropins – contains both FSH & LH, Low dose
• AIM: unifollicular ovulation
( hypogonadal women otherwise normally fertile & at high risk for
multiple pregnancy)
• Luteal phase support with hCG 2,000-2500IU every 3-4 days or
progesterone is needed to compensate for low levels of endogenous LH
that’s insufficient to support normal luteal function.
• Supplemental hcG OHSS.
• Used in women with hyperprolactinemia if they cannot tolerate
dopamine agonist therapy.
29. • Clomiphene resistant anovulation :
• In WHO Group II, gonadotropin levels are normal and in many LH is
high.So treatment is with exogenous gonadotropins on background of
erratic endogenous FSH & LH.
• DOC: r- FSH, low dose
• AIM: Unifollicular ovulation but difficult to achieve.
• Risk of multiple pregnancy & OHSS is high than in hypogonadal
women.
• Luteal phase support is seldom required but in patients receiving
gonadotropin agonist who have poor luteal function , progesterone
therapy is required considering higher risk of OHSS with hCG.
30. Unexplained fertility :
• AIM : Purposeful superovulation. Stimulate the development &
ovulation of more than one mature ovum.
• Superovulation more effective with IUI.
• Higher initial doses can be used as the women ovulate normally & has
no endocrinopathy.
• Any preparation can be used
• Careful monitoring is required.
• Risk of multiple pregnancy is greater
• Luteal support not required because 2 or more corpus lutea yields
supraphysiologic luteal phase serum progesterone concentrations.
31.
32. GONADOTROPIN TREATMENT REGIMENS:
STEP UP REGIMEN:
• In WHO GROUP I & II , ovulation induction begins with low daily dose ( 75IU)
• After 4-7 days of stimulation , sr. estradiol levels provides first measure of
response dose can be maintained / increased as indicated
• Once Sr.estradiol levels rise, USG is done for no. & size of developing follicles
every 1-2 days
• Lead follicle mean diameter of 16-18mm,hCG is given to trigger ovulation
which occurs approx. 36-48 hrs later.
33.
34. LOW- SLOW REGIMEN:
• In women with PCOS, OHSS,multiple pregnancy, cancelled cycles are
avoided
• Dose- 37.5 – 75IU daily, small increments & longer duration of
stimulation( > 7-12 days)
• Insulin resistant women less sensitive to gonadotropin stimulation –
Metformin before & during gonadotropin stimulation improves
response.
35. STEP DOWN REGIMEN:
• Begins with higher dose (150-225IU daily ) & decreases gradually.
• AIM: Promote continued development of only the more sensitive DF
while withdrawing support from less sensitive smaller follicles in cohort.
• ‘COASTING’ -FSH stimulation is withdrawn in latter stages of follicular
development larger follicles continue to function as their LH receptor
expression is receptive to low endogenous LH.,estrogen levels plateau or
decline & smaller follicles begin to regress.
38. • Serum estradiol rise at a constant exponential pace , doubling approx.
every 2-3 days before peak follicular development. A shallower or
steeper slope of increase suggest the need to increase or decrease
the level of stimulation.
• Best results– 500 – 1500 pg/mL
• Ovulation increases with follicular diameter .Risk of multiple gestation
increases with number of follicles likely to ovulate. hCG should not be
given when the risk of multiple ovulation is high & goal is unifollicular
ovulation.
39. • ULTRASOUND MONITORING IN OVULATION INDUCTION :
• Simple, non invasive method which allows for direct visualization
• Base line USG on day 2-3 to determine antral follicular count (b/w size 5-
10mm) and to rule out any ovarian cysts
• TVS scan repeatedly done from day 6-8 ,follicles destined to ovulate will
linearly increase at a rate of 1-3mm/day until it reaches 12mm or upto 18-
24mm, dominant follicle emerges by day 8-12
• HCG is usually administered when there is atleast one follicle measuring 18 to
20 mm, no.of follicles of size 16mm not more than 4 , follicles >12mm not
more than 8 , Sr.E2 not more than 1500-2000pg/ml.
• There is wide range of follicular sizes where it could rupture (13-33mm), mean
diameter 21mm
• So size is poor indicator of imminent ovulation
40. OVARIAN HYPERSTIMULATION SYNDROME :
Iatrogenic complication of ovulation induction with exogenous
gonadotropins.
• Can be observed in clomiphene induced cycles, spontaneous
pregnancies ( multiple pregnancy , molar pregnancy ), germ cell
mutations in FSH receptor.
CLASSIFICATION ACCORDING TO TIME OF ONSET:
1)Early –Occurs within 9 days of oocyte retrieval due to exogenous hCG
trigger
2)Late- Occurs after 10 days of oocyte retrieval due to endogenous hCG
produced by implanting embryo.Its more severe & lasts longer.
41. RISK FACTORS:
a)Young age
b)Low body weight
c)PCOS
d)Higher doses of gonadotropins
e)Previous episodes of hyperstimulation
f) Serum estradiol levels, number of developing ovarian follicles, after
hCG administration
42.
43. GRADE MILD MODERATE SEVERE
1 Abdominal distension & discomfort
2 Features of Grade 1 +
nausea,vomiting and /or
diarrhoea,enlarged ovaries
(5-12cm)
3 Features of mild OHSS & USG
evidence of ascites
4 Features of moderate OHSS + clinical e/o
ascites/ hydrothorax/ difficulty in breathing
5 All + changes in blood volume, increased
blood viscosity due to hemoconcentration,
coagulation disturbance and diminished
renal perfusion and function
44. CLASSIFICATION OF OHSS BY NAVOT:
• SEVERE
• CRITICAL:Thromboembolism , renal failure , ARDS,
hemoconcentration > 55%, leucocytosis , Elevated creatinine &
Creatinine clearance < 50-Need critical care management.
45. TREATMENT:OHSS is Self limiting.Resolves in 10-15days
TYPE OF OHSS OP/IP MANAGEMENT
MILD Conservative .
OP basis.
Close follow up.
Reassurance
Plenty of oral fluids
Avoid exertion.
MODERATE Conservative.
Hematocrit,Electrolytes,I/O record
+Analgesics & anti emetics
Ressessment to be done if there is > in
weight > 2kgs / worsening of symptoms
SEVERE &CRITICAL Hospitalise if :pleural effusion,ascites,
hypotension, severe nausea & vomiting
Hematocrit > 48, K>5 , Na < 135 , Cr> 1.2
Correction of circulatory volume ,
electrolyte imbalance , maintain renal
function , prevention of thrombosis.
Termination of pregnancy , Laparotomy.
46.
47. PREVENTION:
• Rising Sr.estradiol > 2500 pg/mL , many small & intermediate sized
ovarian follicles- high risk indicators
• Cycle cancellation , Less aggressive stimulation in subsequent cycle
• Coasting without further gonadotropin stimulation & delaying
administration of hCG for 1-3 days until estradiol levels plateau or
decline.
• GnRH agonist / r-LH – to trigger endogenous LH surge
• For luteal support , exogenous progesterone.
• Cabergoline – 0.5mg/day starting from day of hCG x 8 days.
• MOA:Dopamine receptor agonist inactivates VEGF receptor
prevents Increased vascular permeability.
48. PULSATILE GONADOTROPIN RELEASING HORMONE:
• Pulsatile IV exogenous GnRH therapy – Artificial hypothalamus
• Anovulatory infertile women with hypogonadotropic hypogonadism,
hyperprolactinemic women
• GnRH pump provides the only instructional signals , the pituitary
gonadotropes are likely to receive.
• Route of administration SC/IV
• IV is given as lower dose 2.5 to 5 µg/pulse every 60-90 min
• SC is given as higher dose 15 to 20 µg/pulse
• Half life is 10 to 40 min after IV dose
• Advantage of GnRH agonists is that they have low risk of multiple
gestation
• Disadvantage is longer duration of IV catherization and daily injections
49. DOPAMINE AGONIST:
Indicated in:
Hyperprolactinemic infertile women with ovulatory dysfunction
Occult hyperprolactinemia -In women with galactorrhoea but normal
prolactin levels ( excess production of biologically active forms of
prolactin not detected in immunoassays , exaggerated nocturnal
prolactin secretion unrecognised in randomly drawn samples) .
Bromocriptine –Stimulates both D1 & D2 receptors,2.5-5mg HS ( some
require 10mg).
Cabergoline –Higher affinity for D2 receptors,0.25 mg twice weekly
,increasing the dose every 4 weeks until women achieve normal
prolactin levels
50. RESULTS :
• Treatment normalises prolactin levels in 60-85% of hyperprolactinemic women.
• Cyclic menses restored in 70-90% within 6-8 weeks
• Ovulatory cycles return in 50-75% of treated women with or without tumors.
• Women with levels >100ng/ml – successful treatment is lower
• Breast secretions diminish in 6 weeks but complete cessation takes about 12
weeks
SIDE EFFECTS:
• More severe during first 2 weeks of therapy .
• Bromocriptine – orthostatic hypotension, nasal stuffiness, dizziness
• To minimise side effects – Start with low dose , taking along with meal , vaginal
route is preferred.
51. LAPAROSCOPIC OVARIAN DRILLING:
• Modern equivalent of classical wedge resection.
• Treatment option for clomiphene resistant ,hyperandrogenic anovulatory
women
AIM:
• Focal destruction of ovarian stroma to decrease both intraovarian &
systemic androgen concentrations
52. PROCEDURE:
• With monopolar 20-30W cutting current ( or analogous setting for
bipolar),vapourize all visible subcapsular follicles.
• 2-4mm depth punctures over capsule ,caution must be taken not to
injure stroma
• 4 punctures in each ovary.
RISKS :
• Postoperative adhesions
• Adverse effects on ovarian reserve
53. TUBAL FACTOR
• Accounts for 25%-35% of infertility
• Non infectious causes – Tubal endometriosis , salpingitis isthmica nodosa, tubal
polyps , tubal spasm , intratubal mucous debris.
• Tubal Infertility & PID- C.trachomatis & N.Gonorrhoea
• Patients with tubal damage with no H/O PID – Subclinical chlamydial infection
• Tubal tuberculosis: calcification of tubes, irregular contour of lumen, diverticular
cavities around ampulla(tufted appearance) and multiple constrictions(beaded
appearance), scarring of tubes (rigid pipe stem)
54. TREATMENT:
PROXIMAL TUBAL OCCLUSION :
• Proximal tubal catheterisation & cannulation performed by HSG / hysteroscopy
restores tubal patency upto 85% of obstructions ( reocclusion rate 30%, pregnancy
rates 12%-44%)
• Catheterisation : passing soft catheter into tubal ostia
• Catheterisation under fluoroscopy during HSG- selective salpingography
• Cannulation : passing guide wire through ostia & injects contrast media /colored
dye.
• Tubal Perforation – 1.9% - 11%
.
55. • Responders: muscle spasm, stromal edema ,amorphous debris,
mucosal agglutination & viscous secretion
• Non responders : Luminal fibrosis, failed tubal reanastomosis ,
congenital atresia , TB, occlusion from salpingitis isthmica nodosa ,
endometriosis, cornual polyp , synechiae
• IVF - if occlusion persists or recurs
• Microsurgical tubocornual anastomosis – excision of tubal isthmus
reimplantation of residual tube into new opening made through
uterine cornua.
56. DISTAL TUBAL OCCLUSION ( Excluding sterilisation or hydrosalpinx)
• 85% of all tubal infertility
• Secondary to infection , endometriosis, prior abdominal or pelvic surgery
• Corrective microsurgery - <35yrs with mild distal tubal disease , normal tubal
mucosa , absent or minimal pelvic adhesions.
• Fimbrioplasty – lysis of fimbrial adhesions or dilation of fimbrial phimosis
• Salpingostomy( salpingoneostomy) –creation of new tubal opening in an
occluded fallopian tube.
• Pregnancy rates – 32%-42% , 54% - 60% , 30%- 34% , 56% for adhesiolysis ,
fimbrioplasty , salpingostomy , nonsterilisation related anastomosis ( ectopic
pregnancy- 7.9%)
• IVF- older patients / patients with diminished ovarian reserve, combined
proximal or distal disease , severe pelvic adhesions , tubal damage which is not
amenable for reconstruction
57.
58. HYDROSALPINX:
• Distal occlusion fluid buildup in fallopian tube hydrosalpinx impedes
embryo development & implantation
• Salpingectomy for hydrosalpinx prior to IVF improves both pregnancy & live
birth rates.
Tuberculosis and infertility:
• Incidence of infertility in tuberculosis ranges from 40 to 75%
• Genital TB is almost always secondary to TB elsewhere in body
• Infertility is caused due to anatomical, physiological and immunological
changes caused by TB
59. ACTIVE TB:
1. Tubal blocks and asherman’s syndrome
2. Tubal damage may lead to ectopic pregnancy
3. Peritubal adhesions and tubo-ovarian abcess
4. chronic endometritis & severe adhesions
LATENT TB:
1. Oophoritis disrupting mechanism of follicular rupture leading to luteinized unruptured
follicle syndrome
2. Mycobacterium inhibits basal production of progesterone and hcg leading to LPD
60. Treatment:
• Medical management forms the mainstay as it eradicates bacterium
• Standard WHO regimen is followed
Surgery is indicated when:
Hydrosalpinx or pyosalpinx
Tubo-ovarian abscess
Pelvic adhesions and peritonitis
Asherman’s syndrome
ART: In case of co existing pelvic factor
61. UTERINE FACTOR
• Pathology with in uterine cavity – 10% of infertility
Anatomical causes Functional causes
Intrauterine adhesions Luteal phase defect
Leiomyoma Non receptive endometrium
Endometrial polyps Integrin deficiency
Adenomyosis
Infections – TB
Congenital uterine defects
62. CONGENITAL ANOMALIES OF UTERUS:
Isolated congenital uterine defects are more often found to be associated
with recurrent pregnancy loss than infertility
Most common congenital defect associated with infertility is septate uterus
Hysteroscopic metroplasty is done for septate uterus
IVF is the treatment option for mullerian agenesis
63. ACQUIRED ABNORMALITIES OF UTERUS
LEIOMYOMAS:
• Pregnancy rates affected by leiomyoma location.
• Removal of cavity distorting Intramural and submucous myomas is done prior to
proceeding with infertility treatment
SURGICAL MEDICAL
myomectomy combined OC pills
hysteroscopic resection progesterone
cryomyolysis GnRH analogs
RU 486
Gestrinone
• Cryomyolysis uses a probe to freeze the tumor, and cause shrinkage and death of
cells
• Selective uterine artery embolisation promote shrinkage of fibroid
64. INTRAUTERINE SYNECHIAE OR ASHERMAN’S SYNDROME
• Severe trauma to basalis layer of endometrium with tissue bridge
formation.
Classification :
Minimal:<25% adhesions involves cavity filmsy adhesions involving fundus
& tubal ostia
Moderate :25 to 70% adhesion of the endometrial cavity, but no
agglutination of uterine wall
Severe :>75% adhesions with agglutination.
• Hysteroscopic resection of synechiae – restores fertility
• This is followed by replenishment of endometrial lining by estrogen
supplementation for atleast 2 months
• IUCD can also be inserted to prevent recurrence
• Risk of placenta accreta for those who achieve pregnancy
66. Luteal phase defect:
• Failure to develop a fully mature secretory endometrium during
implantation
• Inadequate production of progesterone following ovulation , Inadequate
endometrial responsivity to progesterone
• Improper GnRH pulsatality causing insufficient gonadotropin production
during LH surge
• ART & Gonadotropin OI Iatrogenic LPD ( disruption of granulosa cells
from follicular aspiration , suppression of endogenous LH secretion)
Dx:Mid luteal progesterone <5-10ng/mL , delay of 2 or more days in
endometrial histology when compared to chronologic cycle day in 2 or more
cycles , BBT rise lasting less than 11 days , short luteal phase < 14 days
TREATMENT:
Progesterone.
3-4 days following hCG trigger or LH surge & if pregnancy occurs continues
for atleast 8-9 weeks of gestation.
67. PELVIC FACTOR
Endometriosis& Infertility :
Coital function :less frequency , less penetration
Ovarian function: Anovulation , Endocrinopathy – Luteinised unruptured follicle ,
altered prolactin & gonadotropin midcycle surge , oocyte maturation defect
Tubal function : Tubal motility disturbed due to prostaglandins , impaired oocyte
pick up by fimbria
Endometrium :Interference by endometrial antibodies & luteal phase defect
Sperm function : Phagocytosis by macrophages & inactivated by antibody
Increased early abortion
68.
69. Adhesions :
• Result from sharp , mechanical , thermal injury , infection , radiation ,
ischaemia , dessication , abrasion , foreign body reaction.
• Adhesiolysis improves pregnancy rates by 12% at 1 year & by 29% at 2
years in infertile women with adnexal adhesions.
70. CERVICAL FACTOR :
• Cervix stands as the gatekeeper to female reproductive tract, accounts for 3-5% of
infertility
• Characteristics of mucus secreted in pre and post ovulatory phases play an important
role
ETIOLOGY OF CERVICAL FACTOR:
• Cervical scarring or stenosis
1. Post procedures like cone biopsy
2. Electrocauterization
3. LLETZ
4. Cryosurgery
• Chronic infections of cervix destroying the endocervical glands
• Tuberculosis of cervix
• Antisperm antibodies both IgG and IgA
• Acutely retroverted uterus where cervix is not accessible to pool of semen in
posterior fornix
71. TREATMENT OF CERVICAL FACTOR:
• Infection is treated, usually doxycycline 100mg 12th hrly for 2 weeks is given
and both partners should be treated simultaneously
• Mycobacterial infection with antituberculous drugs atleast for 6 months
• Oral mucolytics to thin out very viscid cervical mucus
• Estrogen supplementation from day 8 to 16 for scanty mucus
• ANTISPERM ANTIBODIES: use of barrier contraception x 3 months
• Persistently abnormal cervical factor would require IUI
72. UNEXPLAINED INFERTILITY
• 10-15% of couples diagnosed with unexplained infertility- normal semen
parameters, patent tubes, evidence of ovulation & no other cause.
• Reassurance (after 12 months of failed attempts ,20% conceive in following 12
months , 50 % following 36 months )
• In couples with good prognostic factors of female age < 30 , less than 24 months
of infertility , previous pregnancy with same partner , unexplained infertility
lower extreme of normal fertility
73. LUFS – LUTEINISED UNRUPTURED FOLLICLE SYNDROME
• Luteinisation of a follicle that failed to rupture & release its oocyte , leading to
normal menstrual cycle but infertility.
• 25% of patients with unexplained infertility
• IVF – follicles aspirated, oocytes retrieved , fertilised in vitro.
IMMUNOLOGIC FACTORS
Anti sperm antibodies - 3 strategies
1) Methods to decrease ASA production : Condom therapy( decreases sperm
exposure ) / systemic corticosteroid treatment –mild inflammatory & immune
system suppression.
2) To remove ASA bound to sperm – immune depletion , sperm washing , IgA
protease treatment
3) ART – IUI , ICSI
74. DECREASED ENDOMETRIAL PERFUSION:
Ultrasound based endometrial Doppler studies –abnormal endometrial
perfusion in infertile women
UNDIAGNOSED PELVIC PATHOLOGY :
Following a negative infertility work up , laparoscopy – to evaluate peritubal
adhesions & endometriosis .
OCCULT MALE OR OOCYTE FACTORS:
Occult male factor despite normal semen analysis , oocyte factors – premature
zona hardening , mitochondrial dysfunction , aberrant spindle formation.
75. SUPEROVULATION ( CONTROLLED OVARIAN HYPERSTIMULATION):
• More than one egg to be ovulated( for non-ART or ART purpose) thereby
probability of conception
PROTOCOL:
• Baseline scan on Day 2 of cycle to assess AFC & ovarian cysts & baseline
estrogen & progesterone levels
• CC 100mg x 5 days & Gonadotropins 150-300IU ( maximum
450IU/day)stimulation day 4 or 5 until cycle day 6 or 7 ,when Sr. estradiol level
& TVS are done to document ovarian response.
• Gonadotropin dosage is 50 – 100IU per day every 2-4 days until a response is
evident
• Estradiol levels double every 48 hrs with follicle growth of 1-2mm daily after a
10mm dm is reached
76. • Triggering of Ovulation – 2 follicles reaches 17 – 18 mm & ET- 8mm or more
• For non-nART cycles, Cancellation – if E2 levels – 1000- 2500 pg/mL, 3 or
more follicles – 16mm or more , , 2 or more follicles 14mm or more .
• USG monitoring of IVF cycles without estradiol levels can be considered.
77. TREATMENT OUTCOMES :
• CC & letrozole when combined with IUI – pregnancy rate 18% per cycle
• Combined therapy with gonadotropins& IUI – pregnancy rate 9% per cycle
than superovulation (4%) or IUI( 5%) alone
• Women > 40 yrs –IVF – initial or early treatment plan
• Laparoscopy followed by expected management for unexplained infertility is
cost effective when compared to non- ART treatment or IVF.
• RCT to evaluate optimal treatment for unexplained infertility( FASTT – The
Fast Track and Standard Treatment ) concluded – couples with unexplained
infertility who have not conceived after 3 cycles of CC/IUI should proceed
directly to IVF.
78. INTRAUTERINE INSEMINATION(IUI)
Deposition of spermatozoa in the uterus at any point above the internal
Os.
INDICATIONS:
Unexplained infertility
Cervical factor
Male factor
Ejaculatory failure
Immunological
Endometriosis
79. PREREQUISITES:
• Age< 40 years
• Patient capable of spontaneous or induced ovulation
• One patent fallopian tube with good tuboovarian relationship
• Sperm count > 10million/ml pre wash , > 5 million/ml post wash
• Easy access to uterine cavity
80. STEPS:
1)Ovarian stimulation / induction is performed
2)Serial TVS to monitor follicular growth
3)If spontaneous LH surge has occurred,IUI done within 24 hours of
surge.
4)If spontaneous LH surge has not occurred, Inj.hCG 5000-10000 U IM
given when leading follicle is 18-20mm.IUI performed after 36-40 hours
of hCG.
5)If spontaneous rupture of follicle occurs prior to hCG administration ,
IUI to be done as soon as possible ( IUI should be done 4 hours before or
within 8-12hours of ovulation )
6)Semen collected by masturbation 1 hour 15minutes prior to IUI.
7)Semen wash done immediately after semen collection
81. TECHNIQUE:
1. IUI room should be next to laboratory.
2. Time interval between sample collection & IUI should not be more
than 1 hour & 15min
3. Sterile plastic gloves used instead of latex gloves ( powder of latex
gloves is embryotoxic)
4. Preparation of vagina with NS. Avoid antiseptics as it will kill sperm.
5. Cervix exposed .Avoid holding cervix with Ellis or any other clamp.
6. Flushing IUI cannula with 1-2ml with flushing media washes away
any toxic factors present
82. 7.Insemination volume of 0.6ml -1ml.Minimum concentration of 1
million motile sperms is essential. Good results with 5 million motile
sperms.
8.Deposit the inseminate very slowly into uterine cavity over 3
mins.After the deposit , withdraw the cannula slowly.This prevents
sudden gushing out of the inseminate.
( stop withdrawal halfway, head low, wait for sometime, then withdraw
cannula, compressing both lips of cervix externally)if remaining,deposit
in cervical canal & at external os.
9.Once IUI is completed , speculum removed , head low given , patient
kept on table for 15mins.
83. Difficulties:
• If cannula cannot be passed easily into uterine cavity , anterior lip of cervix
held with ellis.
Cannulas :Makler ,Cook, Tomcat, Edward- Wallace , steel with bulbous tip.
Easy to use, semi rigid, made of non toxic material – Teflon, intracannula
volume is small to minimise deadspace , rounded tips to minimise trauma .
Luteal support given for 14 days.
Dydrogesterone 10mg BD
Micronised progesterone (P/O,P/V) 100mg BD
Inj.Progesterone 50mg IM OD
Inj.hCG 2000units once every 3 days
Antibiotic coverage x 4 days after IUI
Sr.Beta hCG on Day 14 after insemination.
84. ASSISSTED REPRODUCTIVE TECHNOLOGIES
• INCLUDES ALL TECHNIQUES INVOLVING DIRECT MANIPULATION OF
OOCYTES OUTSIDE OF THE BODY
• The ultimate objective of any assisted reproductive technology
program is the birth of a healthy live baby
85.
86. METHODS
• IVF —In Vitro Fertilization
• GIFT —Gamete Intra-fallopian Transfer
• ZIFT —Zygote Intra-fallopian Transfer
• TET —Tubal Embryo Transfer
• POST—Peritoneal Oocyte and Sperm Transfer
• ICSI —Intra-cytoplasmic Sperm Injection
• TESE —Testicular Sperm Extraction
• MESA—Microsurgical Epididymal Sperm Aspiration
87. FACTORS INFLUENCING OUTCOMES
• Etiology of infertility
• Effective controlled ovarian hyperstimulation protocol
• Efficient oocyte retrieval
• Proper embryological laboratory techniques
• Highly receptive endometrial lining
• A very skilled & atraumatic embryo transfer
• Adequate luteal support
• Competent antenatal management
88. IVF
First and most common form of ART.
• OVARIAN STIMULATION
• OOCYTE RETRIEVAL
• SPERM RECOVERY
• FERTILIZATION
• EMBRYO TRANSFER
90. LONG PROTOCOL
Exogenous gonadotropin stimulation after down regulation with a long
acting GnRH agonist
AIM:
• Atleast 2 follicle measuring 17-18mm in mean diameter
• Serum estradiol-200pg/ml per follicle
ADVANTAGES:
• significantly higher rate of egg yields & pregnancy rates
• scheduling flexibility
DISADVANTAGES:
May increase the dose & duration of gonadotropin therapy
91.
92. TREATMENT IN HIGH RESPONDERS
• Cycle cancellation.
• “Coasting” in which GnRH agonist treatment continues but without
further gonadotropin stimulation for 1–3 days, administering hCG
after estradiol levels moderate.
• Proceeding with oocyte retrieval and fertilization but freezing all
embryos in lieu of transfer.
• Delaying transfer until 5 days after retrieval, while observing for
clinical signs and symptoms of developing OHSS.
93. TREATMENT IN LOW RESPONDERS
• The long protocol, beginning with higher doses of gonadotropin
stimulation.
• Decreasing the doses of GnRH agonist or discontinuing agonist
treatment immedIately before or soon after gonadotropin stimulation
begins.
• A short follicular phase GnRH agonist treatment regimen using a
standard or microdose “flare” protocol .
• Using a GnRH antagonist instead of a long-acting agonist.
94. SHORT / FLARE PROTOCOL
• Sequential stimulation with a GnRH agonist & exogenous
gonadotropins
ADVANTAGES-
• improved follicular response
• lower cycle cancellation rates in poor responders
DISADVANTAGES-
• Decreased scheduling flexibility
• significant increase in serum progesterone and androgen levels,
95.
96. GONADOTROPINS+GnRH ANTAGONIST
ADVANTAGE-
• the duration of treatment for an antagonist is substantially shorter
• eliminating the estrogen deficiency symptoms
• the total dose and duration of gonadotropin stimulation required is
decreased
• avoid the risk of stimulating development of a follicular cyst
• Better regimen for pcos & poor responders
DISADVANTAGE-
• Antagonists suppress endogenous gonadotropin secretion more
completely
• pregnancy rates in antagonist treatment cycles may be modestly lower
100. Complication-
• Limited vaginal hemorrhage(8%)
• Acute hemorrhage from ovary & hematomas from injury to uterine ,ovarian, or
illiac vesels(0.04-0.07%)
• Post op pelvic infections(0.3-0.6%)
• Tubo-ovarian abscesses(1-6 wks after retrieval)
EMPTY FOLLICLE SYNDROME ( 0.5–1% )
Characterized by a failure to retrieve oocytes despite apparently normal multi-
follicular development.
101. • A MATURE OOCYTE- (METAPHASE II)
Has extruded the first polar body
Cumulus cells- expanded & luteinized
Corona radiata- sunburst pattern
102. ADV OF MATURE OOCYTES:
Require little preliminary incubation
Inseminated earlier
Better cleavage rate & morphology of oocyte
104. ASSESSMENT :
Evaluated for evidence of fertilization after 18 hrs
Fertilized oocyte: 2 distinct pronuclei & 2 polar bodies
105. EMBRYO TRANSFER
• The goal of embryo transfer is to deliver embryos to the uterus in an
accurate and atraumatic fashion.
• Whenever possible, mucus, blood, and uterine contractions should be
avoided.
• Ultrasound guidance helps to facilitate the insertion of soft catheters,
to confirm correct placement, & to avoid inadvertent trauma to the
fundal endometrium
106.
107.
108. LUTEAL SUPPORT
• Progesterone- 1)orally (300–800 mg daily),
2) vaginally(90 mg daily),
3) cream or tablet (100–600 mg daily),
4) intramuscular injection (25–50 mg daily;
• Supplemental doses of hCG every 3 days (1500–2500 IU)
• Duration of treatment- until 7 wks of gestation
109. ICSI
• Assisted fertilization technique developed to circumvent the need for
sperm to penetrate the zone pellucida.
• Other methods- drilling, partial zona dissection & subzonal insertion
or insemination
• Indication-
1. male factor infertility- severe oligospermia,asthenospermia,
teratospermia
2. Surgically retrieved sperms
3. Plan for PGD
4. Previous failed /poor fertilization with conventional IVF
5. High titers of antisperm antibodies
111. Gamete Intrafallopian Transfer (GIFT):
• Eggs retrieved from a woman mixed with sperm & immediately
replaced in one or other of the woman’s fallopian tubes so that they
fertilise inside the body.
• Used in people with unexplained male factor fertility problems-
Transcervical embryo transfer is impossible.
Zygote Intrafallopian Transfer (ZIFT):
• Eggs fertilised outside body & then transferred into the fallopian
tubes.
• Not widely practised.
• Developed alongside IVF using much of the same technology.