Docstoc

Lipids Online Slide Master - onofriescu.ro

Document Sample
Lipids Online Slide Master - onofriescu.ro Powered By Docstoc
					Partnership Between the Patient, the
ObGyn, and the Fertility Specialist




      ObGyn      Patient    Fertility
                           Specialist




                                        1
There Are Multiple Causes
of Infertility
                                     Causes of Infertility
                                               14%
                    18%                                                        Tubal factor

                                                                               Ovulatory dysfunction
                                                        6%
                                                                               Diminished ovarian reserve

                                                                               Endometriosis
                                                           6%
                                                                               Uterine factor
           13%
                                                                               Male factor
                                                           7%
                                                                               Other causes
                                                         1%
                                                                               Unexplained
                11%
                                                                               Multiple female factors

                           6%                  19%                             Multiple factors male + female




Centers for Disease Control. http://www.cdc.gov/ART/ART02/sect2_fig14-24.htm#Figure%2014. 2006.
                                                                                                                2
Assisted Reproductive Technology (ART)
     Infertility treatment options   • Weight management
                                     • Surgical interventions
                                     • Pharmacologic interventions


                                     •   Ovulation induction (CC)
         In vitro fertilization      •   Ovulation induction (gonadotropin)
                                     •   Controlled ovarian stimulation protocols
                                     •   ICSI

                                     • Preimplantation genetic diagnosis
       Associated technology         • Cryopreservation
                                     • Oncology considerations



                                     • Pregnancies/deliveries IVF
           Efficacy of ART           • Pregnancies/deliveries ICSI
                                     • Rate of complications



                                     •   Need for partnership
             Partnership             •   Management algorithm
        for better outcomes          •   Recommendations
                                     •   Transition of patient
                                                                                    3
Treatment Options for Female Infertility
● Weight management
● Surgical interventions
    – Tubal reconstruction/flushing
    – Adhesiolysis, salpingectomy, laparoscopic treatment of endometriosis
    – Correction of uterine abnormalities
● Pharmacologic interventions (non–ovulation induction)
    – Selective estrogen receptor modulators, insulin-sensitizing agents, aromatase
      inhibitors, etc
● Ovulation induction
    – Natural or intrauterine insemination


● Assisted reproductive technologies
    – In vitro fertilization
         • Controlled ovarian stimulation
         • Intracytoplasmic sperm injection




                                                                                      4
Managing Obesity in Women Can
Improve Fertility
                                              2.0
                                                                                            1.7%
               Odds ratio for subfertilitya




                                              1.5                               1.4%


                                                    1.0%        1.0%
                                              1.0



                                              0.5



                                               0
                                                    <18.5   18.5 to <25.0   25.0 to <30.0   ≥30

                                                                   BMI (kg/m2)
aTime   to pregnancy >12 months.
Ramlau-Hansen et al. Hum Reprod. 2007;22:1634.
                                                                                                   5
Weight Loss as Treatment for Infertility
                PCOS
               BMI >25                 Anthropometric and
                                                                                                    1.0




                                                                Rate of regular cycles, ovulatory
         Anovulatory infertility       echographic evaluation




                                                                     cycles, and pregnancy
             Diet 1200 kcal
                                                                                                    0.8                    Ovulatory cycles



         BMI reduction by 5%           Anthropometric and
                                                                                                    0.6
             then by 10%               echographic evaluation
                                                                                                                  Regular menstrual
                                                                                                    0.4                cycles
      Ovulation       Anovulation

                                                                                                    0.2                      Pregnancy
Residual time for
spontaneous conception
                                                                                                     0
                    End of the study                                                                      0   2      4        6       8       10
                                                                                                                    Months

        Treating obesity appears to reinstate normal ovulatory functions

Crosignani et al. Hum Reprod. 2003;18:1928.
                                                                                                                                               6
Tubal Reconstruction
● Tubal reconstruction appears less effective than IVF for
  treatment of tubal factor infertility
      – Series of 83 women with distal tube occlusion treated surgically and
        followed for 1 year1
            • Pregnancy within 1 year: 15.7%
            • Live births from the above pregnancies: 9.6%
      – Overall delivery rate per transfer for IVF patients with tubal
        factor: 28.9%2




1. Nichols and Steinkampf. Prim Care Update Ob Gyns. 1998;5:168.
2. Benadiva et al. Fertil Steril. 1995;64:1051.
                                                                               7
Adhesions Can Affect Infertility
                 Origin                                             Effects
● Endometriosis                                       ● Distortion of tubo-ovarian
                                                        relationships, preventing ovum
● Pelvic inflammatory disease                           capture
  (PID)
                                                      ● May hinder oocyte
● Peritoneal infections
                                                        development and maturation
     – Appendicitis
                                                         – Decreased ovarian blood
     – Tuberculosis                                        supply
● Surgery                                                – Inadequate delivery of
                                                           gonadotropins and growth
                                                           factors to follicles




Diamond and Freeman. Hum Reprod Update. 2001;7:567.
                                                                                         8
Uterine Structural Abnormalities
● Congenital abnormalities
  (Incidence %)
       –   Hypoplasia/agenesis (n/a)
       –   Unicornuate (6.2%)
       –   Bicornuate (20.3%)
       –   Didelphys (6.2%)
       –   Arcuate (32.8%)                    Didelphys


       –   Septate (33.6%)

● Endometrial polyps
● Myomas (fibroids)




Taylor and Gomel. Fertil Steril. 2008;89:1.
Raga et al. Hum Reprod. 1997;12:2277.
                                                          9
Uterine Abnormalities, Reproductive
Effects, and Common Treatments
                                          Effects on
  Abnormality                            Reproduction       Treatment
  Congenital Uterine
  Abnormalities
   Unicornuate                    45% loss of pregnancies   Removal of rudimentary horn by
                                                            laparotomy or laparoscopy
   Bicornuate                     45% loss of pregnancies   Rarely requires surgical treatment
   Didelphys                      42% loss of pregnancies   Resection of vaginal septum, Strassman
                                                            reunification
   Septate                        79% loss of pregnancies   Hysteroscopic resection
  Polyps                             28% pregnancy rate     Polypectomy
  Myomas                                      -             GnRH agonist, mifepristone, uterine
                                                            artery embolization, myolysis,
                                                            myomectomy



Taylor and Gomel. Fertil Steril. 2008;89:1.
                                                                                                     10
Possibly Useful Pharmacologic
Interventions
● Selective estrogen receptor modulator
  (clomiphene/tamoxifen)—antagonizes estrogen
  feedback activity at hypothalamic-pituitary axis
● Insulin-sensitizing drugs
  (metformin/troglitazone)—insulin resistance
  may play a key role in the pathogenesis of
  ovarian dysfunction
● Aromatase inhibitor (letrozole)—blocks
  conversion of androstenedione and
  testosterone to estriol and estradiol

Stadtmauer et al. Fertil Steril. 2001;75:505.
Mitwally and Casper. J Soc Gynecol Investig. 2004;11:406.
                                                            11
Indications for In Vitro Fertilization
● Absent or blocked fallopian tubes
● Failed tuboplasty
● Concomitant pelvic disease
● Severe male factor infertility
● Endometriosis
● Diminished ovarian reserve
● Unexplained infertility
  – Failed intrauterine insemination (IUI)
Diedrich et al. Hum Reprod. 1992;7(suppl 1):115.
                                                   12
Ovulation Induction
● Useful in patients with anovulatory infertility as well as
  unexplained infertility
     – WHO class I: hypogonadotropic hypogonadism
     – WHO class II: PCOS

● Goal
     – Stimulate development of a single follicle that will be able to
       reach preovulatory size and rupture

● Options
     – Clomiphene citrate (CC)
     – Gonadotropins (LH, FSH, gonadotropin-releasing hormone
       [GnRH], human chorionic gonadotropin [hCG])


Messinis. Hum Reprod. 2005;20:2688.
                                                                         13
Pharmacology of Clomiphene
Citrate (CC)
● Nonsteroidal triphenylethylene derivative
● Binds to estrogen receptors (ER) throughout the
  reproductive system
      – Both agonist and antagonist properties
      – Efficacy in ovulation induction attributed to binding to hypothalamic
        ER
      – Increases both LH and FSH
      – Considered best initial treatment for the majority of women whose
        infertility is associated with ovulatory dysfunction

● Some deleterious effects on endometrium and cervical
  mucous (due to systemic antiestrogen effects)

Practice Committee of the American Society for Reproductive Medicine. Fertil Steril. 2006;86(suppl 5):S187.
Sereepapong et al. Fertil Steril. 2000;73:287.
                                                                                                              14
Standard CC Treatment Regimen
                                                           5 days Coitus
                                                                  every other day
                                                           7 days




                                                  5 days
                                             50-250 mg/d
                                             Clomiphene


                                                                           Progesterone




                                      LH

                                     FSH

                                       2 4 6 8 10 12 14 16 18 20 22 24 26 28 30
                                   Menses         Clomiphene therapy


Home Fertility Network. Ovulation induction. http://www.homefertility.com/ovulind.htm. 2007.
                                                                                               15
Efficacy of CC: Meta-Analysis of
Clinical Results

                                        69.4%
                             70
                             60
             % of patients




                             50
                             40
                             30
                             20
                                                                                 8.8%
                             10                              6.2%

                              0
                                  Ovulation per cycle Pregnancy per cycle   Pregnancy per
                                                                            ovulatory cycle




Steiner et al. Hum Reprod. 2005;20:1511.
                                                                                              16
CC Summary
● Simplest initial treatment for majority of women
● Reported outcomes are variable, but in general, pregnancy
  rates 6% per cycle
● Limit treatment to 6 (3 if poor ovulation induction) cycles
  (low probability of success beyond this)
● Monitor patients to ensure effectiveness of ovulation
  induction (basal body temperature, urinary LH, serum
  progesterone)
● Principal risk associated with CC is multifetal gestation
  (<10%)
Practice Committee of the American Society for Reproductive Medicine. Fertil Steril. 2006;86(suppl 5):S187.
National Institute for Clinical Excellence. http://www.nice.org.uk/nicemedia/pdf/CG011fullguideline.pdf. 2004.
Hanson and Dumesic. Mayo Clin Proc. 1998;73:681.
Imani et al. J Clin Endocrinol Metab. 1999;84:1617.
                                                                                                                 17
Gonadotropin Therapy
● Represents a more physiologic approach to multifollicular
  recruitment than CC
● Agents
   – Purified or recombinant human FSH
   – Human menopausal gonadotropins (hMG): 75 IU each of FSH
     and LH
   – Human chorionic gonadotropin (hCG)
● Gonadotropin preparations constitute the principal agents for
  ovulation induction and COS
   – Significantly higher odds of pregnancy per woman (OR=0.41,
     95%CI: 0.17-0.80) vs antiestrogen induction
   – Maximum control
      • Ovarian response
      • Risk of multiples

Davis and Rosenwaks. Sem Reproductive Med. 2001;19:207.
Athaullah et al. Cochrane Database Syst Rev. 2002:CD003052.
                                                                  18
Ovulation Induction:
Gonadotropin Treatment
● Starting dose of FSH usually 50 or 75 IU
● Increments of 25-50 units after 7-14 days
● May include IUI or natural intercourse
                       OI



                                                     hCG




Homberg and Insler. Hum Reprod Update. 2002;8:449.
Lambalk et al. Hum Reprod. 2006;21:632.
                                                           19
Ovulation Induction vs In Vitro Fertilization
● Ovulation induction (OI)
  – Goal: induce growth of 1 or 2 mature follicles
  – Low doses of gonadotropins
  – Clomiphene citrate (CC)
  – Natural insemination or IUI fertilization
● In vitro fertilization (IVF)/COS
   – Goal: induce growth of multiple mature follicles
   – Higher doses of gonadotropins
   – Oocytes removed, fertilized in laboratory setting,
     then returned to uterus


                                                          20
In Vitro Fertilization (IVF)
               Procedure                                                          Risks
● Initially used in women with fallopian                      ●    Ovarian hyperstimulation syndrome
  tube blockage or damage                                          (OHSS)
                                                                     –   Usually not serious and resolves with
● Now employed for many causes of                                        outpatient management
  infertility (eg, endometriosis, male                               –   1%-2% severe requiring hospitalization
  factor)                                                            –   Dose-dependent, avoided by careful
                                                                         titration
● Involves
                                                              ●    Anesthesia
      – Controlled ovarian stimulation (COS)
      – Egg retrieval                                         ●    Multiple births
      – Insemination, fertilization, embryo                   ●    Ectopic pregnancy
        culture
      – Embryo transfer                                       ●    Psychologic distress
      – Cryopreservation of extra embryos



American Society for Reproductive Medicine. http://www.asrm.org/Patients/patientbooklets/ART.pdf. 2008.
                                                                                                                  21
Typical IVF Protocol
      Controlled
        ovarian
      stimulation




                                                                  Embryo
         Follicular aspiration                                cryopreservation
                                                               PGD screening


                                    IVF
                                     or
                                   ICSI

     Oocyte freezing                              Embryo
                                                  cleavage

                                                             Embryo          Pregnancy
                                                             transfer        diagnosis


Oehninger. J Soc Gynecol Investig. 2005;12:222.
                                                                                         22
Key Concepts in Controlled Ovarian
Stimulation
● Prospective identification of ovarian response
  (high, intermediate, low)
● Individualization of treatment
● Prevention of complications by careful dose
  titration:
   – Ovarian hyperstimulation syndrome (OHSS)
● Optimization of the total reproductive potential
  by embryo cryopreservation


Arslan et al. Fertil Steril. 2005;84:555.
                                                     23
Gonadotropin Releasing Hormone (GnRH)
● Released from the hypothalamus in small amounts
  about once every 90 minutes
● Stimulates the pituitary gland to secrete LH and FSH
● A GnRH analogue often is used to prevent spontaneous
  ovulation when gonadotropins are given to women
  undergoing IVF
   – Agonists
      • Leuprolide, nafarelin, goserelin, buserelin,
        deslorelin, triptorelin
   – Antagonists
      • Ganirelix, cetrorelix
American Society for Reproductive Medicine. http://www.asrm.org/Patients/patientbooklets/ovulation_drugs.pdf. 2006.
van Loenen et al. Semin Reprod Med. 2002;20:349.
                                                                                                                      24
Native GnRH
   pGlu   His   Trp   Ser   Tyr   Gly   Leu   Arg   Pro   Gly
                                                                NH2


● Synthesized and secreted in the hypothalamus
● Released in coordinated pulses by the hypothalamus
● Reaches the pituitary via the HP portal system
● Stimulates the release of FSH, LH, and GnRH
  receptors of the anterior pituitary
● Quickly metabolized with a half-life of <5 minutes




                                                                      25
Controlled Ovarian Stimulation (COS):
Gonadotropin Treatment
● Starting dose of FSH usually 150 or 225 IU
● Needs GnRH analogue treatment to prevent premature
  LH surge
● Ovarian stimulation followed by oocyte pick-up, in vitro
  fertilization, and transfer of embryos

                          COS


                                                           hCG




Arslan et al. Fertil Steril. 2005;84:555.
Borini and Dal Prato. Reprod Biomed Online. 2005;11:283.
Yong et al. Fertil Steril. 2003;79:308.
                                                                 26
Potential Adverse Effects of
Gonadotropin Treatment
● Deliveries after IVF and ICSI combined are multiple
      – Twins: 21.7%
      – Triplets: 1%
● Premature delivery
● OHSSa
● Breast tenderness
● Swelling or rash at the injection site
● Abdominal bloating and/or pain
● Mood swings

aDose-dependent.

Andersen et al. Hum Reprod. 2008;23:756.
American Society for Reproductive Medicine. http://www.asrm.org/Patients/patientbooklets/ovulation_drugs.pdf. 2006.
                                                                                                                      27
Typical GnRH Agonist Protocols
                         Long follicular protocol                                        FSH
                                                                                     Agonist

                          Cycle day M     3    5    7    9    11   13
                                                                                                    hCG

                         Long luteal protocol                                            FSH
                                                                                     Agonist

                          Cycle daya 15   17   19   21   23   25   27   M    3   5   7   9     11
                                                                                                    hCG

                         Short/flare-up protocol                                         FSH
                                                                                     Agonist


                                                                                                    hCG
                         Ultrashort protocol                                             FSH
                                                                        Ag
                                                                        Ag


                                                                                                    hCG

                         Early cessation protocol                                        FSH
                                                              Agonist


                                                                                                    hCG

aPrior   cycle.
 van Loenen et al. Semin Reprod Med. 2002;20:349.
                                                                                                          28
GnRH Antagonist Protocols

                                                   FSH
                 Single-dose protocol
                                                   Antagonist


                                                            hCG


                 Multiple-dose protocol            FSH
                                                   Antagonist


                                                            hCG




van Loenen et al. Semin Reprod Med. 2002;20:349.
                                                                  29
 Antagonist Protocol Is Shorter Than
 Agonist Protocol
                                                       hCG
                          Day 2 or 3
                          of menses     Day 6 of FSH           Embryo transfer
                                           GnRH antagonist

Cycle day
                                         rFSH
  21-24                                                       IVF
                                                                           Luteal phase
                                                               or            support
                        GnRH agonist
                                                              ICSI
                                         rFSH


                      Downregulation

     Luteal phase (prior cycle)                              Luteal phase (current cycle)

                       Start of cycle
                                                                                            30
GnRH Agonists vs Antagonists: No
Difference in Live-Birth Outcomes
              Citation         Year       0.01        0.1     1          10      100   Effect   P Value
              Albano           2000                                                     0.83     0.56
              European         2000                                                     0.75     0.12
              Olivennes        2000                                                     0.80     0.61
              North American   2001                                                     0.78     0.32
              Middle East      2001                                                     0.97     0.91
              Akman            2001                                                     0.76     0.71
              Hohmann          2003                                                     0.93     0.86
              Martinez         2003                                                     1.57     0.59
              Franco           2003                                                     0.55     0.57
              Hwang            2004                                                     1.11     0.87
              Sauer            2004                                                     1.07     0.91
              Xavier           2005                                                     0.85     0.76
              Loutradis        2005                                                     0.70     0.47
              Malmusi          2005                                                     1.00      1.00
              Marci            2005                                                    10.36      0.06
              Cheung           2005                                                     1.55     0.64
              Check            2005                                                     1.82     0.35
              Barmat           2005                                                     0.65      0.36
              Bahceci          2005                                                     0.84     0.60
              Badrawi          2005                                                     0.80      0.64
              Schmidt          2005                                                     1.00     1.00
              Lee              2005                                                     0.70     0.52
                                                                                        0.86     0.08

                                             Favor agonists       Favor antagonists


Kolibianakis et al. Hum Reprod Update. 2006;12:651.
                                                                                                          31
GnRH Agonists vs Antagonists:
Other Outcomes

    Outcome                                           Difference (Antagonist vs Agonist)

    Duration of treatment                              Shorter for antagonist (difference >19 days)

    FSH requirement                                                   No difference

    Oocytes retrieved                                 Lower for antagonist (difference 1.2 per cycle)

    OHSS associated with hospital admission             Lower with antagonist (odds ratio = 0.46)

    LH surge                                            Higher with antagonist (odds ratio = 4.05)

    LH rise                                             Higher with antagonist (odds ratio = 8.27)




Kolibianakis et al. Hum Reprod Update. 2006;12:651.
                                                                                                        32
Intracytoplasmic Sperm Injection (ICSI)
                                                                          Success Rate and
    Indications
                                                                          Complications
●   Very low numbers of motile sperm
                                                                     ●    Fertilization rate: 50%-80%
●   Severe teratospermia
                                                                     ●    Live offspring: 20%-40% (40% in
●   Problems with sperm binding to and                                    younger women, success declines
    penetrating the egg                                                   with maternal age)
●   Antisperm antibodies
●   Prior or repeated fertilization failure with
    standard IVF methods
●   Frozen sperm limited in number
    and quality
●   Obstruction of the male reproductive tract not
    amenable to repair




American Society for Reproductive Medicine. http://www.asrm.org/Patients/FactSheets/ICSI-Fact.pdf. 2001.
Palermo et al. Sem Reprod Med. 2000;18:161.
Campbell and Irvine. Br Med Bull. 2000;56:616.
                                                                                                             33
Oocyte Retrieval
● Transvaginal ultrasound-guided oocyte retrieval (TVOR) during IVF
  treatment is the gold standard for IVF therapy1,2
        – May be performed without general anesthesia
        – Generally well tolerated

● Complications1
        – Aspiration needle injury to adjacent pelvic organs and structures leading to
          serious complications1
        – Infection3
        – Hemorrhage3
        – Adnexal torsion3
        – Rupture of endometriotic cysts3
        – Hyperprolactinemic stress when performed under general anesthesia4
        – Vertebral osteomyelitis3
1.   El-Shawarby et al. Hum Fertil (Camb). 2004;7:127.
2.   Yuzpe et al. J Reprod Med. 1989;34:937.
3.   Bennett et al. J Assist Reprod Genet. 1993;10:72.
4.   Robinson et al. Hum Reprod. 1991;6:1291.
                                                                                         34
Preimplantation Genetic Diagnosis
(PGD) and Screening
              Indications                             Evaluations
● Recurrent miscarriage or                     ● Mosaicism
  unsuccessful IVF cycles
                                               ● Chromosome aberrations
● Unexplained infertility                         – Aneuploidy
                                                  – Structural chromosome
● Advanced maternal age
                                                    aberrations
● Male factor infertility                         – Reciprocal translocations
                                                  – Robertsonian translocations
● Fertile couples carrying single
                                                  – Inversions
  gene disorders
                                                  – Deletions
                                                  – Duplications
                                                  – Genomic imprinting and
                                                    uniparental trisomy
                                                  – Single gene disorders

Kearns et al. Semin Reprod Med. 2005;23:336.
                                                                                  35
ESHRE Consensus Meeting on Genetic
Risks and Complications in ART
● Both partners should be examined (female by a gynecologist, male by
  an andrologist)
● All couples with severe male subfertility or repeated fertilization failure
  should be counseled by a genetically trained specialist
● Genetic counseling should be offered
● Possible laboratory testing
      – Chromosomal analysis and microdeletion testing in nonobstructive
        azoospermia and oligozoospermia
      – Karyotype is suggested when sperm count is <5 million/mL and highly
        recommended when sperm count is <1 million/mL
      – Cystic fibrosis transmembrane regulation (CFTR) gene analysis in
        congenital bilateral absence of the vas deferens and related conditions
      – In pregnancy, mid-trimester ultrasound screening for congenital
        malformations and amniocentesis may be considered
Land and Evers. Hum Reprod. 2003;18:455.
                                                                                  36
Common PGD Single-Gene Testing
Most common PGD single-gene tests performed
● Autosomal dominant
   – Myotonic dystrophy = 35%




                                                Image courtesy of David Hill. Ph.D.
   – Huntington disease = 29%
   – Charcot-Marie-Tooth = 8%
   – Other = 29%
● X-linked
   – Fragile X = 26%
   – Duchenne/Becker muscular dystrophy = 23%
   – Hemophilia = 9%
   – Other = 42%
● Autosomal recessive
      – Cystic fibrosis = 38%
      – Thalassemia = 18%
      – Spinal muscular dystrophy = 17%
      – Other = 27%
Kearns et al. Sem Reprod Med. 2005;23:336.
                                                                                      37
Two Basic Techniques Developed for
Cryopreservation
                             Slow Freezing                     Vitrification
                                              Physiologic
                                              solution
               Before                         Cryoprotectant
               cooling                        solution

                                              Vitrification
                                              solution


                                              Ice seeding

                After                         Slow cooling                 Rapid cooling
               cooling


                                              Rapid cooling



               In LN2


Kasai and Mukaida. Reprod Biomed Online. 2004;9:164.
                                                                                           38
Pregnancy and Deliveries After IVF in
Europe (2004)

                           40                                      Pregnancies
                                                                   Deliveries
                           35
                                                                 30.1%
                           30                   26.6%
           % of patients




                                24.1%
                           25
                                                                         21.1%
                                                        18.8%
                           20           17.4%
                           15
                           10
                            5
                            0
                                 Per cycle      Per aspiration   Per transfer




Andersen et al. Hum Reprod. 2008;23:756.
                                                                                 39
Pregnancy and Deliveries After ICSI in
Europe (2004)
                                                              Pregnancies
                     40
                                                              Deliveries
                     35
                                                            29.8%
                     30                    27.1%
                          25.1%
     % of patients




                     25
                                                                    19.8%
                     20           17.2%            18.4%

                     15
                     10
                      5
                      0
                            Per cycle      Per aspiration    Per transfer



Andersen et al. Hum Reprod. 2008;23:756.
                                                                            40
Complications and Fetal
Reductions With ART in Europe (2004)
                            (From 29 countries, 785 clinics reported 367,066 cycles)
                     3000     2858

                             (0.77%)
                     2500
  Number of cases
  (incidence rate)




                     2000

                     1500
                                           1125
                     1000                  (0.30%)
                                                       520                               526
                      500                                         362
                                                     (0.14%)                            (0.14%)
                                                                 (0.09%)       4
                        0
                             OHSS         Oocyte     Bleeding   Infection   Maternal     Fetal
                                         retrieval                           death     reduction
                                       complications




Andersen et al. Hum Reprod. 2008;23:756.
                                                                                                   41
Assisted Reproductive Technologies:
Summary
● Improvement in knowledge and technology has
  made it possible to optimize ovarian
  development, retrieve and fertilize oocytes, and
  preserve embryos with a minimal risk to patient
● Despite all these advances, younger maternal
  age has the most successful impact on
  outcomes




                                                     42
How can the ObGyn and fertility specialist together
make sure that patients get the most appropriate
treatment as soon as possible?




        ObGyn           Patient      Fertility
                                    Specialist




                                                      43
Management Algorithm for ObGyn
                                                    Couple attempting conception


 Female <35 years of age                                                                                        Female >35 years of age
 1 year of infertility                                                                                          6 months of infertility
                                   Determine progesterone level 7 days after presumed ovulation
                                                                                                                            Ovulation
                                          Anovulation or oligo-ovulation without hirsutism
                                                                                                                       Consider referral for
                                                                                                                              COS
                                         Female physiology: serum sensitive TSH, FSH, and
                                         prolactin levels                                            Abnormal


                                                                Normal                                                   Refer to fertility
                                                                                                                         specialist

                                                    Male evaluation: semen analysis                  Abnormal


                                              Female anatomy: hysterosalpingography                  Abnormal


                                Treatment: clomiphene citrate 50-100 mg/d orally for 5 days during
                                menses, for 3 cycles

                                                                                      Unsuccessful
                                Successful

                           Initiate prenatal care



Hanson and Dumesic. Mayo Clin Proc. 1998;73:681.
                                                                                                                                               44
Lifestyle Changes Can be
Recommended
● Avoid smoking and secondhand smoke to
  improve fertility (both male and female)
  and to reduce required dose of fertility
  medication
● Lose weight
● Reduce stress



Kelly-Weeder and O’Connor. J Am Acad Nurse Pract. 2006;18:268.
Younglai et al. Hum Reprod Update. 2005;11:43.
                                                                 45
Reasons for Referral to
a Fertility Specialist
● Factors indicating immediate referral to a
  fertility specialist
   – Older female age
   – Tubal occlusion
   – Abnormal semen parameters
   – Insulin resistance
   – Abnormal ovarian reserve testing
   – CC failure
   – Suspected or confirmed infertility

Potter. http://www.infertilityspecialist.com/acrobat/The%20Contemporary%20Fertility%20.pdf. 2008.
Olive and Hammond. Postgrad Med. 1985;77:205.
                                                                                                    46
Transition From Clomiphene Citrate (CC) to
Specialist-Guided Therapy and Back
● CC is widely used for ovulation induction in women with
  PCOS and in couples with unexplained infertility to
  induce follicular development
● Because of the potential side effects associated with
  CC, all patients should be monitored to assess
  response to treatment
● Without ultrasound monitoring, the number of CC
  cycles should probably be limited to 3 (or less), and
  early referral should be considered
● After successful ART, transition of patient back to
  ObGyn and prenatal care should be initiated
PCOS = Polycystic ovary syndrome.
Case. Can Fam Physician. 2003;49:1465.
                                                            47
Summary
● Infertility treatment protocol depends on female age
● Conduct diagnostic tests after
  – 1 year of infertility for female aged <35 years
  – 6 months of infertility for female aged >35 years
● Refer to fertility specialist after 3 (or fewer)
  unsuccessful CC cycles




                                                         48

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:2
posted:4/19/2013
language:Unknown
pages:48