The Female Factor
NATIONAL JOURNAL OF HOMOEOPATHY 2003 Mar / Apr VOL V NO 2.
Dr CH Asrani
Identifying the male factor is simple as it is based on semen
analysis alone. Female factor by comparison is complex as it involves the
following: (see fig)
1. The woman must be ovulating (ovulatory factor)
2. It must pass through the tube (tubal factor)
3. Sperm must enter the cervix after having survived the environment of vagina (cervical factor)
4. fertilized ovum must be implanted properly in the endometrium
Isn’t it complex? Also, before we plan a couple’s
investigations, age is to be taken into consideration. Those over 35 need an
aggressive approach.
Initial Infertility Evaluation:
Complete history and physical examination. All previous
medical records for treatment related to infertility, hormonal and/or menstrual
disturbances, anovulation, gynecologic surgery, or pelvic infection. Appropriate
medical information should be gathered on the husband.
Evaluation of Ovulation: A woman who is getting regular,
normal menstrual cycle, is in all probabilities ovulating regularly. Great
variation in number of days between menstrual periods is a sign of an error
somewhere in the hormonal axis and is usually anovulatory. Basal Body
Temperature charts from up to 3 months may be reviewed. While patients may be
encouraged to initially record BBT. These charts have retrospectively value in
determining that the patient has in fact ovulated but of little value predicting
when ovulation has occurred.
Ultrasonography Serial Ultrasonography studies from 14th
to 18th/19th day are done to monitor
the growth and rupture of a follicle. Most commonly used method for ovulation
profile nowadays
Hormone levels- we know the intricate, well
co-ordinated role hormones play in the menstrual cycle. If a woman gives history
of delayed/irregular cycles, hormonal assay may form first line of
investigations.
Initial Hormonal Evaluation-Initially one should ask for
FSH/LH; TSH, Prolactin, and mid luteal, morning progesterone levels. The last,
if above 10 ng/ml, suggests normal ovulation. (Progesterone levels may drop up
to 50% by the afternoon and after a meal.)
Laboratory testing in special groups:
Over 35: FSH, LH with ratio and estradiol obtained on
cycle day 3. A ratio of FSH:LH more than 4 is diagnostic of PCOD (Poly Cystic
Ovarian Disease). Clomiphene Citrate 50 mg OD is given from 1st
to 5th day for ovulation induction.
Irregular Menses: DHEAS should be obtained. Values above
250 ug/dl, although still in the normal range, may be seen in patients with
Polycystic Ovarian Disease. These patients usually benefit from Metformin
therapy.
Irregular cycles with Hirsutism, Acne or Obesity: In
addition to FSH:LH and ratio, Fasting insulin and glucose is recommended. If the
fasting insulin:glucose ratio is over 0.25 or the insulin level is over
10miu/ml, referral is indicated as many of these PCOD patients benefit from Metformin
or Pioglitazone therapy.
Tubal Infertility:
Once it has been confirmed that a woman is ovulating
normally, next to be suspected are the fallopian tubes that transport the egg to
the site of fertilization. The tubes may be blocked or restricted in their
movement due to adhesions. In patients with NO history of pelvic pain, surgery,
dysmenorrhoea or dyspareunia chances of tubal factor being responsible are quite
remote.
Risk Factors for Tubal factor:
- Dyspareunia
- Previous pelvic surgery
- IUD complications such as removal for pain, bleeding or infection
- History of PID
- Recent onset Dysmenorrhoea, if associated with pelvic tenderness, uterosacral nodularity or perimenstrual diarrhoea, should be considered evidence of endometriosis.
Laparoscopy can reveal adhesions from previous infection that may be blocking the tubes, as well as more subtle adhesions outside the tube that could interfere with their ability to pick up the ovum. Laparascopy can allow one to examine the surface of the ovaries to see if there is scarred appearance, which suggests that ovulation is not occurring. Furthermore, laparascopy is the only way of making a firm diagnosis of endometriosis. Such endometrial implants are a major cause of infertility. Laparoscopy can also be used as a confirmatory procedure by injecting a dye into the uterus through the cervix and observing whether the dye spills freely through the tube into the abdomen. Sometimes tubes that appear to be blocked on HSG are shown really to be open on laparascopy.
Cases Warranting Special Consideration:
1. Age over 35, > 3 years infertility & risk
factors (+): Laparoscopy or IVF should be considered early in the
evaluation. Tubal patency should be determined preoperatively to rule out
proximal tubal obstruction which can be treated during an initial laparoscopic
procedure.
2. Low risk factors, anovulatory infertility or AID candidates: After an initial HSG, ovulation induction or AID (donor insemination) may be considered for 3-4 cycles before considering diagnostic laparoscopy or IVF.
If the woman is ovulating and has patent tubes, the following 2 tests are commonly done but are not conclusive.
- Post-coital testing has not been shown to correlate well with fertility and therefore is rarely indicated.
- Endometrial Biopsy: The routine use of endometrial biopsy to confirm the adequacy of luteal phase has poor predictive value for the management of infertility and is only indicated for those patients with regular cycles and recurrent pregnancy loss. Endometrial biopsy therefore is not indicated in the diagnosis of infertility.
Initial couple friendly approach:
- Empirical Treatment: Female patients are treated with prenatal vitamins. Both male and female partners are treated with doxycyline 100 mg BID for presumed ureaplasma infection. Prevalence of this infection is > 35% and treatment costs roughly one-tenth the cost of culture evaluation. Males are started on Vitamin C 1,000mg daily.
- Preconception Counseling: The risks of genetic abnormalities are discussed for those with a family history or age > 35. Smoking cessation, alcohol reduction, weight loss, marital counseling are recommended as indicated. Males are encouraged to avoid hot tubs, saunas, steam baths and hot baths.
OVULATION:
1. Anovulation (non PCOD, < 35 years old, FSH<10
miu/ml) Clomiphene 50 mg is administered from cycle day 3 through 7. An
ultrasound is obtained to evaluate:
- Is there adequate follicular development (follicle size > 20mm)
- Is the endometrium adequate (<6mm with mature 20mm follicle)
For patients with discrepant results on ultrasound the following options should be considered. For those with follicular size of 20mm and endometrium of 6mm or less, an estradiol value is obtained. If a 14-18mm follicle is seen with an endometrium of 6mm or more, you can assume follicular growth of 2-3mm/day and administer hCG 10,000 units IM in 1-2 days.
Satisfactory ovulation can be confirmed with a midluteal, morning progesterone above 10 ng/ml. Therapy is continued for three cycles. If the patient does not conceive, intrauterine insemination (IUI) is recommended 24 hours after the LH surge is detected, or 36-42 hours after hCG is administered. This can be carried out for not more than three additional cycles.
2.Anovulation (PCOD): Women who have evidence of PCOD are best managed by Metformin, or Pioglitazone therapy combined with a low-processed carbohydrate diet and exercise. If Metformin is not tolerated, patient refuses or regulation of the menstruation does not occur after three months on Metformin therapy, then ovulation with injectable gonadotropins should be considered.
A patient is considered for Metformin or Pioglitazone therapy if she has 8 or less cycles per year AND any of the following:
1. Failure to respond to clomiphene,
2. Fasting insulin above 10miu/ml,
3. Elevated androgens,
4. Acanthosis nigricans,
5. Family history of diabetes,
6. Polycystic ovaries on transvaginal ultrasound.
Metformin is started at 500mg daily with a meal and increased to 500mg twice daily after the first week. One week later the dose is increased to 850mg bid. Patients should be pre-screened with a serum creatinine level and should discontinue the medication approximately 48 hours prior to surgery or an IVP dye X-ray. Metformin is discontinued if urine pregnancy test is positive. If the patient fails to regulate cycles after three months of therapy consideration is given to continuing an additional three months, adding/switching to Pioglitazone, low dose clomiphene or injectable gonadotropin therapy.
2. Hyperandrogenic PCOD patient scheduled for Laparoscopy: Ovarian drilling may be performed at the time of laparoscopy. Small follicular cysts should be punctured and drained at the time of laparoscopic surgery with up to 10-12 punctures per ovary. Alternatively, a Yag or KTP laser is used. Ovulation occurs in 50-60% with pregnancies reported in up to 50%. The beneficial effect may be short lived.
Hyperprolactinemia: MRI is usually reserved for those with symptoms or those with prolactin values above 100 ng/ml. Suppression of prolactin level is initiated with Bromcriptine therapy at 1.25mg(1/2 tablet) HS for one week. This is increased to BID during the second week. During the third week, 2.5mg is taken HS and 1.25 mg in the morning and finally during the fourth week, 2.5 mg is taken BID. A repeat fasting prolactin level is obtained, 1 week after the full dose is reached. If the level is not suppressed, dose may be increased to 2.5 mg TID if the patient is able to tolerate. Patients frequently experience postural hypotension, dizziness, and GI distress. If regulation of the menstrual cycle is not achieved after two-three months of normal prolactin levels, clomiphene therapy may be initiated.
