The infertile couple

A. Initial visit

   Complete medical, surgical & gynecologic history

 . Specifically, information regarding menstrual cyclicity, pelvic pain, obstetrical history

. Risk factor for infertility - PID, IUD use, pelvic surgery, intrauterine exposure to   DES,  pituitary, adrenal & thyroid function

 . Male partner - genital surgery, infection, trauma, history of mumps

 . Coital frequency, dyspareunia, sexual dysfunction

 Physical exam - particular attention to height, weight. body habitus, hair distribution, thyroid gland, galactorrhea and pelvic examination

Etiology and Management of each factor:

      1.Male factor:  Etiology :

Defects in Semen production ( Spermatogenesis): due to:

a. Hypothalamic disturbances   as In Kallman syndrome (Anosmia + GnRH)

           b. Pituitary diseases                  as In Hyperprolactinemia

                                                Three. Testicular defects                       as In Klinefelter – Orchitis- Undescended testis-                                                                              

                                                Four. Varicocele, TB, Syphilis, and tumours     

Defects in Semen passage: As in bilateral obstruction of the epididymis, vas deferens or ejaculatory duct. The obstruction may be congenital, inflammatory as gonorrhoea or trauma (as hernia operation or sterilisation)

Defects in Semen deposition: May be due to impotence, or vaginismus

Investigations of the male factor:

1. Semen analysis:     Normal Semen: ( WHO criteria ):

Volume            2-5ml               Liquefaction time          within 30 minutes

Concentration               >20 million/ml

Motility             >50% Progressive motility

Morphology                 >30% normal forms

White blood cells                      <1 million/ml

Abnormal Semen:

                        Azoospermia:   Complete absence of spermatozoa

                        Oligospermia:   Decreased number of spermatozoa

                        Necrospermia:  All spermatozoa are dead

                        Teratospermia:Abnormal forms of spermatozoa exceeding 70%

2. Hormonal assays: 

            In the presence of oligo and or asthenospermia, the following should be measured: FSH-Testosterone- Prolactin

3. Testicular biopsy:

            A testicular biopsy should be performed in cases of azoospermia to differentiate between functional or obstructive azoospermia.

Sperm penetration assay     Measure the ability of sperm to undergo capacitation to fuse with & penetrate the oocyte membrane & to undergo nuclear decondensation

Golden hamster's egg - treated with enzyme to remove the cumulus & zona pellucida.  Sperm are placed in protein-rich environment which promote capacitation.  Zona-free eggs are exposed to sperm.  presence of one or more swollen sperm heads within the oocyte demonstrate              penetration

Prognostic value of SPA - controversial, does not discriminate between fertile & infertile

Treatment: 

Andrological consultation should be requested:

1-Hormonal treatment:

GnRH analogues for Kallman syndrome

Other medications not proven to be of value as clomiphene citrate and HCG

Antisperm antibodies:

Condoms

Moderate to high dose corticosteroids

Intrauterine insemination of washed spermatozoa

IVF

1.      Non obstructive azoospermia:

Micromanipulation with the new artificial reproductive technology as the TESA and the PESA

2.      Surgical management:

As Surgical correction of the obstructive azoospermia

Varicocele Ligation

Protocol of Management

Mild male Factor  

step 1    Expectant management (three cycles)

Step 2   Intrauterine insemination with or without clomiphene citrate (three cycles)

Step 3   Intrauterine insemination with injectable gonadotropin therapy (three cycles)

Step 4  In vitro fertilization with or without intracytoplasmic sperm injection (six-cycle maximum)

Moderate Male Factor

Step I: Intrauterine insemination with  ovulation induction (three cycles)

Step II: In vitro fertilization with or without intracytoplasmic sperm injection (six-cycle maximum)

Severe Male Factor    intracytoplasmic sperm injection

Artificial insemination

Encompasses a variety involving placement of whole semen or processed sperm into the female reproductive tract : permits sperm-oocyte interaction in the absence of intercourse

Type of insemination : intracervical, intrauterine, intraperitoneal, intrafollicular insemination,  fallopian tube sperm perfusion

Processing semen

          Washing

          Separation procedure : centrifugation through density gradients , sperm migration protocols, differential adherence procedure

Phosphodiesterase inhibitors (pentoxiphylline) : enhance sperm motility, fertilization capacity, acrosome reactivity for IVF procedures

Sperm retain their fertilizing capacity for 24-48hr after ejaculation if they are able to escape the intravaginal environment, oocytes can be fertilized for approximately

12-24hr after ovulation

ii.Success rate

               Under 30 years of age no other infertility factors : conception rate approach

               40% after 12cycles of treatment

Female factor:  This includes

Tubal factor

Uterine factor

Cervical factor

Peritoneal factor

Tubal factor of infertility

Incidence:                     12-33% of cases of infertility

Etiology:          

Congenital       hypoplasia or aplasia of the tube

                  Inflammatory:    The most commom cause of secondary infertility

Pelvic inflammatory disease (puerperal, postabortive, chlamydial, tuberculous or gonococcal)

                                          Pelvic peritonitis

Endometriosis   Leading to pelvic adhesions with kinking and obstruction of the  tube

                  Neoplastic        Bilateral cornual fibroid

Damage most significant for fertility includes

1.destruction of the delicate tissues and folds that line the inside of the fallopian tubes (the mucosa and rugae),

2.occlusion of the distal end of the fallopian tube,

3.dilatation of the fallopian tube with the presence of an inflammatory liquid (exudate) within the lumen of the tube (hydrosalpinx), and

4.extratubal adhesions that may distort the normal course of the tube within the pelvis.

History & Examination:- (of little help as infections may be subclinical)

1-History of repeated attacks of pelvic pain, gonorrhoea

2-History of previous pelvic surgery

3-Examination may show adenxal mass

Investigations:

These are conducted to preview tubal patency:

Tubal insufflation is no longer regarded as an accurate test for tubal patency and has been replaced by Hysterosalpingography and laparoscopy

These two tests not only test the tubal patency but also provide different information that may be used in the evaluation of infertility. HSG gives information about the uterine cavity that a laparoscopy and dye test cannot provide, whereas laparoscopy gives information about the rest of the pelvis including peritubal adhesions, endometriosis, and ovarian pathology.

One.Hysterosalpingography:

Two.The test is done 4-7 days after menstruation

Three.It is usually performed with no anesthesia however some nervous women will require an anaesthetic.

Four.Bimanual examination is done to determine the uterine position and to exclude pelvic lesions

Five.A self-retaining vaginal speculum is applied to expose the cervix, which is painted with antiseptic lotion and grasped with a volsellum.

Six. The cannula is introduced into the cervical canal

Seven.A radio opaque substance is injected into the uterus through the cannula on the X-ray table (lipidol, 40% iodine in Poppy-seed oil). 

Eight.To avoid oil embolism we can use a water-soluble medium (urograffin), but this is rapidly absorbed and may not show peritubal adhesions.

Nine.An X ray is take immediately after the injection to show the uterus and tubes.

Another film is taken after 24 hours in case of lipidol and after 10-30 minutes in case of urograffin to show peritoneal spill.

Advantages of Hysterogram:

1.      It shows the site of obstruction of the tube

2.      Diagnosis of peritubal and pelvic adhesions

3.      Diagnosis of uterine abnormalities

4.      It gives less false negative results than tubal insufflation which was used in the past (shows higher incidence of patent tubes) as lipidol pressure is more efficient to overcome tubal spasm.

Contraindications:

1.      Infection in the vagina, cervix, uterus or tubes.

2.      Tenderness on bimanual examination, which may indicate silent infection that, will flare up after injection.

3.      Presence of menstruation or bleeding to avoid embolism.

4.      During amenorrhea as the patient may be pregnant.

5.      In the premenstrual period to avoid:

Embolism                                             endometriosis

False negative results                            Disturbance of possible pregnancy

6.General diseases that contraindicate pregnancy as heart failure

Complications:

1-Pain and shock may occur

2-Ascending infection as salpingitis and peritonitis (risk is less than 1% however in high risk poplation it may reach 3%

3-Oil embolism if lipiodol was used

4-Endometriosis particularly if the test is done premenstrual when the endometrium is thick that fragment may detatch and implant in the peritoneal cavity or other pelvic organs.

5-Cervical lacerations or perforation of the uterus by the sound or cannula

6-Disturbance of a possible pregnancy.

False positive results :

1. Spill from phimotic fimbrial end

2. Free pelvic dissemination from unilateral tubal patency may give an impression of bilateral patency

3 Localised consriction in a tortous hydrosalpinx

False negative results :

1. Leakage of the dye                       2. Cornual spasm

3. Large uterine cavity or localised intrauterine synechiae .

4. Faulty techique e.g.embedding of the cannula in the cervix

Intravasation :

Cannula used :

By whatever method used the dye should be injected slowly so that abnormalities of the uterine cavities are not missed , this is important in DES-related anomalies.

- Classic Jarcho cannula with a single toothed tenaculum

- Pediatric Foley catheter through the cervix into the uterus . This is relatively a traumatic but the ballon of the catheter may obsecure myoma or polyp

- Suction apparatus attached to the cervix and the dye injected through a contained cannula

Pelvic infection and HSG :

- The overall risk of infection with HSG is probably < 1% although in a high-risk population serious infection can occur in about 3% of cases .

- If there is a history suggestive of PID , a sedimentation rate is obtained prior to the HSG and , if elevated , antibiotic therapy is given . The procedure can be then postponed for a month when repeat when a repeat ESR is obtained and only if normal HSG is scheduled

- If masses or tenderness are revealed by pelvic examination , HSG could be bypassed and the pelvis evaluated by laparascopy

- In patients with a questionable risk of infection , a water soluble rather than an oil dye should be used because of the faster absorption .

- Routine prophylactic antibiotics are preferred by many clinicians : doxycyclin 100 mg b.i.d. for 5 days , begining 2 days before the procedure .

Special problems : 

1. Pain and cramping : use of Pg synthetase inhibitor can be given 30 min. before the HSG . If this occurred during the procedure the injection should be stopped for few minutes and flouroscopy temporarily discontinued followed by slow injection

2. If the tubes fill but the dye droplets do not spill from the fimbriated ends , the tubes are put under stretch by pushing the uterus up in the abdomen .

Therpeutic value :

1. Dislodging mucus plugs (mechanical lavage)

2. Breaking peritoneal adhesions by staightening of the tubes

3. Stimulatory effect for the tubal cilia

4. Bacteriostatic effecy of iodine on the mucous membranes

5. Decreased in vitro phagocytosis of peritoneal macrophages

Laparoscopy:

This is inspection of the pelvic cavity through an endoscope passed through the abdominal wall.  This investigation is now very frequently performed, but it does carry risks, which must be taken into account

The patient is anaesthetized, the bladder emptied, a cannula and forceps fixed to the cervix.  This allows the uterus to be moved about once the endoscope is passed, and dye can be injected through the cannula to test the patency of the tubes.

Advantages:

q                 It shows the site of tubal obstruction.

q                 It shows peritubal and pelvic adhesions

q                 It shows other pelvic pathology as endometriosis

q                 It shows the ovaries and external surface of the uterus.

q                 It differentiate between similar pictures in HSG as septate and bicornuate uterus

q                 It allows the therapeutic intervention

Falloposcopy

          Direct observation of the lumen of the fallopian tube via laparoscopy or hysteroscopy

          can define normal tubal appearance & has identify abnormal mucosal tubal patterns :

          tubal ostial spasm, presence of intraluminal debris as a cause of tubal obstruction

Classification:-

(1) Mild disease

           1.absent or small (less than 15 mm diameter) hydrosalpinx (dilatation),

           2.easily recognized fimbria (the delicate finger like structures emerging

             from the distal end of the tube) that were inverted prior to repair

             (reopening of the distal tube),

           3.absence of significant peritubal or periovarian adhesions, and

           4.normal rugae of the inner tube on HSG.

        * (2) Moderate disease

           1.a hydrosalpinx with a 15-30 mm diameter,

           2.fragments of fimbria that are not easily recognized,

           3.periovarian or peritubal adhesions without fixation of these structures,

           4.minimal adhesions in the cul de sac behind the uterus, or

           5.absence of tubal rugae on HSG.

        * (3) Severe disease

           1.large hydrosalpinges (greater than 30 mm diameter),

           2.absent fimbria,

           3.dense adnexal adhesions with fixation of the ovary and tube, or

           4.obliteration of the cul de sac behind the uterus

Treatment:

The treatment of tubal factor of infertility depends on the extent of the tubal damage and whether surgical management can be done or not.

1st. Surgical management:

This can be done either laparoscopically or by a laparotomy and in the latter case microsurgery should be better conducted.

The major principles involve the use of magnification over the range of 2X to 60X, minimal tissue handling, the use of atraumatic instruments such as glass rods to handle tissues, the use of fine (6-0) non reactive suture materials, keeping tissues moist with warm saline, proper hemostasis using bipolar coagulation. What is the value of these for the undergraduate?      

Distal tubal disease:

            Salpingolysis:    Cutting adhesions lateral to the tube

            Salpingostomy:

Proximal tubal disease:

            Tubal resection and end to end anastomosis

            Tubo cornual anastomosis

            Isthmic anastomosis     

            Trans cervical tubal cannulation

B. In vitro fertilization in case of extensive tubal damages (25% success rate per treatment per cycle).

IVF Protocol

        1.GnRH agonist downregulation is performed prior to ovulation induction with

          gonadotropins

        2.Follicular maturation and ovulation are effected with combined hMG/hCG

          administration

        3.Oocyte retrieval is performed transvaginally under ultrasonographic guidance

        4.Analgesia for oocyte retrieval is provided on an individualized basis but most commonly involves intravenous sedation or spinal nerve block

        5.Embryo transfer is undertaken 48hr after oocyte retrieval - transcervical cannulation  and injection of embryos into the intrauterine cavity

        6.Luteal phase support is provided until menses or pregnancy is documented

         Initial evaluation for pregnancy - quantitative B-hCG measurement 16days after

         embryo transfer

        There are several reports of improvement in IVF pregnancy rates after removal

        of hydrosalpinges (dilated tubes). The widely accepted belief is that liquid

        within the blocked dilated fallopian tubes has no alternative but to pass into the

        uterine cavity and the presence of this fluid disrupts the ability of an embryo to

        implant.