Speculum Examination |
Postcoital Test |
Case: 27 year old G0 with irregular intermittent (on and off) bleeding throughout the month for the past 2 years and a prior history of regular menstrual intervals every 27-28 x 3-4 days.
Question: What should be considered given this information?
Answer: The history of intermittent (on and off) vaginal bleeding with a variable amount of flow (ranging from spotting to heavy with clots) suggests several possibilities.
- The area immediately outside of the vaginal vault (the vulva) may be the source of bleeding (from infection, trauma, lesion on the skin).
- The vaginal vault may bleed from trauma, foreign bodies, inflammation, malignancy, or endometriotic implants.
- The uterine cervix may bleed from a polyp, erosion, malignancy or infection.
- There may be pregnancy related tissues within the uterine cavity that can bleed. The uterine cavity can also bleed from a foreign body like an IUD, an endometrial polyp, a fibroid, adenomyosis, malignancy, or a hormonal imbalance.
- The ovary may be producing estrogen from a tumor (such as a granulosa cell tumor).
- The non-gynecologic organs in the vicinity may also bleed and the bleeding may be “assumed” to be coming from the vagina, including the urinary tract and the bowel.
- Certain medications may cause bleeding and certain blood disorders may result in excess bleeding.
A diagnostic management plan should be developed in order to identify the source of bleeding. A complete history and physical examination (H+P) can often be performed relatively quickly and the H+P is invaluable since it can exclude many of the possible causes of bleeding immediately. Laboratory tests including bloodwork and radiologic tests should be selected after obtaining the H+P.
Case: 39 year old G0 with a history of regular menstrual intervals every 28-30 x 4 days, a constant feeling of fullness within the vaginal vault, some difficulty with sexual intercourse with the husband stating that he seems to be “hitting something” in the vagina during thrusting, no change in regular bowel movements, and no loss of urine with coughing or sneezing.
Question: What should be considered given this information?
Answer: The history of fullness within the vaginal vault and the husband’s complaint about something in the vagina during intercourse suggests several possibilities. The vagina may be filled by an aborting uterine myoma that has been “delivered” through the uterine cervix and remains attached to the uterine cavity. The entire uterus may be “dropping” from its usual location within the pelvis through the vaginal vault and on rare occasion the uterus can even be seen to be extending through the vaginal orifice (opening). Constipation can cause the fecal material within the bowel to protrude into the vagina so that there is a noticeable bulge in the posterior wall of the vagina. There may even be a foreign body in the vagina, such as a tampon that has somehow been forgotten.
In this situation, a vaginal speculum examination may be able to identify the cause of the feeling of “fullness” in the vagina. An aborting myoma should generally be removed surgically. A descending or prolapsing (dropping) uterus often follows multiple childbirths and is associated with “stress urinary incontinence” (often presenting as an involuntary loss of urine with coughing or sneezing) and can be corrected surgically. Constipation can be treated with a change of diet, additional fiber supplementation within the diet or medication while impacted stool (fecal material) sometimes needs to be expressed manually. Foreign bodies can often be removed upon identification.
Case: 32 year old G0 a history of subfertility (trying for just over a year without a pregnancy), regular menstrual intervals every 27-29 x 5-6 days, and a husband with unproven fertility (no prior pregnancies) and no semen analysis. During the initial “history and physical examination” a vaginal speculum examination using a medium sized Graves speculum appears to be uncomfortable.
Question: What should be considered given this information?
Answer: A vaginal speculum examination is an important component of the physical (gynecologic) examination of a female with infertility problems. This speculum examination should not ordinarily be uncomfortable.
Many women bring (their own set of) concerns to the physical examination. Some women have had painful or embarrassing experiences during previous exams. Other women may want to get to know the doctor (over the course of a few consultations) or have a plan of action (diagnostic testing and treatment alternatives) fully developed so that they are comfortable with the office (couples undergoing infertility treatments often seek 2nd or 3rd opinions along the way). An adequate pelvic examination generally requires a relaxed patient.
During a pelvic examination the doctor should be as gentle as possible and when possible (s)he should watch the patient’s face for signs of discomfort. Vaginal speculums do come in different shapes and sizes, with the most common shapes being “Graves” (duckbill shaped) and “Pedersen” (straight and narrow). If a medium sized Graves speculum is uncomfortable due to its shape or size, then switching to a Pedersen or a smaller Graves speculum may be all that is required.
Case: 31 year old G0 with a history of regular menstrual intervals every 28-29 x 4-5 days, a normal hormone evaluation (TSH and Prolactin concentration), a hysterosalpingogram revealing a normal uterine cavity and bilateral tubal patency, and a husband with unproven fertility (no prior pregnancy) yet a normal semen analysis. A postcoital test is planned.
Question: What should be considered in order to prepare for this postcoital test?
Answer: The timing of the postcoital test (the day that it is performed) is very important. The cervical mucus quickly responds to the (sex steroid) hormones estrogen and progesterone. Estrogen generally enhances the quantity and quality of cervical mucus while progesterone generally has the opposite effect. Estrogen is normally greatest 1-2 days prior to ovulation and progesterone normally has a very low concentration prior to ovulation. Therefore, the cervical mucus is thought to be “friendliest” to sperm within a day or two before ovulation. Once ovulation occurs, the progesterone concentration rises rapidly and the cervical mucus becomes forbidding (hostile) to sperm.
Ovulation most often occurs about 14 days prior to the onset of the next menstrual flow. Therefore, if the woman has very regular menstrual intervals every 28-29 days ovulation would be expected on about day 14-15. When the menstrual history is so regular one can make a relatively good “guess” at the time of ovulation and time the postcoital test within a few days of expected ovulation. In this case, the postcoital test could be scheduled on either cycle day 12 or 13.
If the menstrual history is not so regular, then ovulation detection is useful in determining the optimal day for the postcoital test. I generally have suggested the use of the commercially available home ovulation predictor kits that are designed to detect the LH surge (which has an onset about 36 hours or a day and a half prior to ovulation). I try to perform the postcoital test on the day of or the day after the initial positive ovulation kit result (if the kit turns color = positive on a Tuesday then I suggest performing the postcoital test that Tuesday or Wednesday).
Case: 26 year old G0 with a history of irregular menstrual intervals every 1-4 months, a normal hormone evaluation (TSH and Prolactin concentration), a hysterosalpingogram revealing a normal uterine cavity and bilateral tubal patency, and a husband with unproven fertility (no prior pregnancy) yet a normal semen analysis. Clomiphene citrate (clomid or serophene) is used for ovulation induction (to shorten the intermenstrual intervals) with ovulation for this woman generally around cycle day 19 on medicated (clomid) cycles. A postcoital test is performed on a clomid cycle and a scanty (small) amount of thick viscous mucus is found to have 0-3 non-motile sperm per high power field.
Question: What should be considered in this situation given this postcoital test result?
Answer: Clomiphene citrate is often effective at reducing intermenstrual irregularity and the duration of time between the onset of flow and ovulation. Therefore, clomiphene was worth trying for this patient (with irregular cycle intervals every 1-4 months) and actually the medication does appear to be effective.
Clomiphene citrate acts predominantly by binding cellular estrogen receptors for long periods of time (which consequently results in a down regulation of these receptors). Thus, on clomiphene citrate the circulating estradiol concentration may be very high while the tissue’s estrogen receptor concentration may be very low. This downregulation of estrogen receptors in peripheral tissue results in “the body” not being able to detect circulating estrogen. The inability to detect and respond to estrogen leads to the side effects associated with clomiphene citrate, particularly those characteristics of hypo-estrogenemia (hot flashes, mood swings, insomnia).
Cervical mucus is a highly dynamic substance that becomes “friendly” to sperm (immediately) prior to ovulation largely in response to (heightened) estrogen. When examining the cervical mucus of women during cycles of ovulation induction with clomiphene citrate I often find that the cervical mucus is reduced in quantity (scanty), thickened, and less elastic than expected. Postcoital test results during clomiphene citrate cycles are also (consequently) abnormal more often than otherwise expected. This is most likely due to the “anti-estrogen” effects of the clomiphene citrate on the cervical mucus. Therefore, I suggest a postcoital test for all of my patients on clomiphene citrate and when the postcoital test is abnormal then I also suggest intrauterine inseminations (IUIs) timed around ovulation.
In this case example, the postcoital test is abnormal on clomiphene citrate so I would suggest IUIs. The use of supplemental estrogen as a treatment for the abnormal cervical mucus during clomiphene citrate cycles is almost always ineffective since there is no real lack of estrogen (just a reduction in estrogen response due to a reduction in cellular estrogen receptor concentration).
Case: 38 year old G0 with a history of regular menstrual intervals every 28 x 4-5 days, a normal hormone evaluation (TSH and Prolactin concentration) and encouraging ovarian reserve (basal FSH and estradiol concentration), a hysterosalpingogram revealing a normal uterine cavity and bilateral tubal patency, and a husband with proven fertility (two prior pregnancies in a previous marriage) and a normal semen analysis. A postcoital test is performed revealing normal appearing cervical mucus (amount, cellularity, elasticity) with 6-7 motile sperm per high power field that all appear to be “wiggling in place.”
Question: What should be considered in this situation given this postcoital test result?
Answer: I am generally encouraged when I find greater than 5 motile sperm per high power field on postcoital test. However, the “quality of movement” of the motile sperm is also very important. I am most reassured when the sperm is moving rapidly and progressively across the field of view. Sperm with slow progressive movement is also acceptable since the sperm may not yet have undergone capacitation (a stage of sperm development after ejaculation during which sperm characteristically become hypermotile). Sperm “wiggling in place” is often associated with the presence of antisperm antibodies (male or female) since the sperm become adherent to the antibodies, which then immobilize that region of the sperm (eg., as if caught by the tail).
There are elegant tests commercially available to detect the presence and type of antisperm antibodies. However, the results (of these antisperm antibody tests) rarely alter my treatment plan so I rarely suggest them. Rather, if there is a significant abnormality in the postcoital test (such as the bulk of the sperm wiggling in place) then I simply recommend intrauterine inseminations (IUIs). The IUIs place the sperm above the cervical mucus (where complement mediated immobilization of sperm often occurs) and is sometimes effective. If ineffective, then I reconsider more aggressive treatment (such as In Vitro Fertilization) with assisted fertilization.
Case: 35 year old G0 with a history of regular menstrual intervals every 27-28 x 4 days, a normal hormone evaluation (TSH and Prolactin concentration), an encouraging assessment of ovarian reserve (basal FSH and Estradiol concentration), a normal postcoital test, and a husband with unproven fertility (no prior pregnancy) yet a normal semen analysis is scheduled for a hysterosalpingogram.
Question: What should be considered in order to prepare for this radiologic test?
Answer: Many women talk with their female friends about the tests that are normally performed during an infertility evaluation. Often, the hysterosalpingogram (HSG) is described as (unbelievably) painful by those who have had the test. I believe that virtually all of the pain that can be experienced during a HSG is avoidable if the test is performed in a specific (patient considerate) manner. I offer to perform this test myself for all of my own patients so that I can decrease their exposure to (unnecessary) discomfort as well to allow me to see the entire study (in progress) so that I can get all of the information possible from the test.
I routinely suggest prophylactic antibiotics for an HSG examination to minimize the risk of infection (especially reactivation of a dormant infection within the reproductive tract). If the woman has no allergy to doxycycline or tetracycline then I usually order doxycycline 100mg by mouth every 12 hours (starting the evening prior to the HSG) x 4 doses.
I also suggest 600 - 800 mg of ibuprofen (motrin) by mouth (if there is no allergy to the medication) with some food about 30-60 minutes prior to the HSG to minimize the sensation of uterine cramping. When I perform the study, I inject the radioopaque dye into the uterine cavity very slowly so that I can (1) see the contour of the uterine cavity in a very early film (which increases the sensitivity of the study to enhance my ability to identify small intrauterine lesions) and (2) minimize the uterine reaction to the dye (to reduce cramping due to uterine muscle contractions during the study).
It is rare for a woman to describe the HSG as painful when I perform the study myself and I take the precautions as described above.
Case: 27 year old G0 with a history of regular menstrual intervals every 30 x 4-6 days, a normal hormone evaluation (TSH and Prolactin concentration), a normal postcoital test, and a husband with unproven fertility (no prior pregnancy) and a normal semen analysis. A hysterosalpingogram (HSG) is scheduled and performed on cycle day 9. One week after the HSG is performed, the patient complains of persistent vaginal bleeding and is found to be pregnant with a quantitative hCG titer of 15,000 IU/L. Two days later the hCG concentration is found to be 9,000 IU/L. On ultrasound examination there is an irregular (probably collapsed) gestational sac without any evidence of embryonic development (a fetal pole or heart beat).
Question: What should be considered in this situation?
Answer: Hysterosalpingogram testing is normally scheduled 6-13 days after the onset of a menstrual flow. This timing is intended to (1) avoid pregnancy (since the test is performed prior to ovulation), (2) avoid pushing endometrium that is sloughing as the menstrual flow into and through the tubes (which theoretically could increase the chance of proximal tubal occlusion or subsequent endometriosis), and (3) avoid “false positive” findings within the uterine cavity secondary to blood clots or menstrual debris (which may be present during active flow).
The HSG test does involve flouroscopy with radiation to the region of the uterus and is contraindicated during pregnancy due to the potential for causing a spontaneous pregnancy loss or fetal abnormalities. Nevertheless, I am not aware of any radiologic center or hospital (offering HSG testing) that requires or even routinely suggests a urine pregnancy test immediately prior to the study.
Bleeding in early pregnancy is not uncommon. The amount and timing of the vaginal bleeding can be mistaken for a “normal menstrual flow”. Therefore, I generally suggest to my own patients that they perform a urine pregnancy test the day prior to (or the morning of) a hysterosalpingogram even when they have a history of regular menstrual intervals and a “normal appearing” last menstrual period within 13 days of the study. This should effectively eliminate the possibility of performing an HSG inadvertently during pregnancy since the commercially available urine (home) pregnancy tests (USA) are sensitive to about 20-50 IU/L and the hCG titer of a normal pregnancy at 4-6 weeks gestation should be (roughly) between 100 to 20,000 IU/L.
In this case described, the hCG titers suggest that the woman was pregnant during the HSG test and that she is now undergoing a spontaneous pregnancy loss (with the hCG titers declining and the appearance of the collapsed gestational sac on ultrasound examination). A discussion between the physician and the patient should review the risks and benefits of a dilatation and curettage versus awaiting a completed spontaneous loss. In these situations (as with any early pregnancy), one should also maintain a high index of suspicion for an ectopic pregnancy.
Case: 33 year old G0 with a history of regular menstrual intervals every 30-31 x 5-6 days, a normal hormone evaluation (TSH and Prolactin concentration), an encouraging assessment of ovarian reserve (basal FSH and Estradiol concentration), a normal postcoital test, and a husband with unproven fertility (no prior pregnancy) yet a normal semen analysis. This woman is known to have a retroflexed (“tipped”) uterus. A hysterosalpingogram is scheduled.
Question: What should be considered in order to obtain the most amount of information from this radiologic test?
Answer: About 90% (9 out of 10) of women have an anteflexed uterus (the body of the uterus is angled anteriorly towards the abdominal wall in relation to the cervix) and about 10% (1 out of 10) of women have a retroflexed uterus (the uterine body has a backward or posterior angulation in relation to the cervix while the cervix maintains its usual position). Reflexion of the uterus is a variant of normal (rather than a pathologic finding) and has no known association with subfertility.
When a woman with either a severely anteflexed or severely retroflexed uterus is lying flat on her back, the uterine cavity is pointed upward (anteflexed) or backward (retroflexed) such that it appears to be “all bunched up” on itself during a hysterosalpingogram (HSG). That is, the cavity is superimposed on itself when viewed under flouroscopy during the HSG such that subtle lesions in the uterine cavity may be more easily missed (the sensitivity of the procedure with respect to identifying lesions in the uterine cavity is significantly reduced). In these circumstances, it is helpful to gently pull down on the uterine cervix (with an attached tenaculum) during the HSG so that the entire uterine cavity is more easily seen. Often radiologists are uncomfortable with placing a tenaculum on the uterine cervix or moving the uterus during the test. This is another reason why I offer to perform the procedure for my own patients.
Case: 24 year old G0 with a history of regular menstrual intervals every 26-28 x 3-5 days, a normal hormone evaluation (TSH and Prolactin concentration), a normal postcoital test, and a husband with unproven fertility (no prior pregnancy) yet a normal semen analysis. This patient has a history of abnormal pap smears and she has had cervical cyrosurgery (“freezing”) twice and a LEEP procedure. At this time she has an unusual shaped uterine cervix that appears scarred around the opening to the vaginal vault (the external os). A hysterosalpingogram (HSG) is scheduled.
Question: What should be considered in order to prepare for this radiologic test?
Answer: The radioopaque dye used during the HSG is most often instilled (entered) into the uterine cavity using a catheter attached to a syringe. Some of the catheters that are used are actually fed through the cervix into the uterine cavity (at which point a small balloon can be inflated to hold the catheter in place) and others have an acorn shaped tip that can be held in place while being tightly apposed to the outer (external) uterine cervical os (opening). Generally a tenaculum is clamped to the outer upper lip of the cervix when the acorn tip catheter system is used.
I prefer the acorn tip catheter system to perform a HSG for several reasons. Often, in women with a prior history of cervical surgery (which is currently a common treatment for some abnormalities that can be seen on pap smear) the cervix is scarred and possibly stenotic (containing a stricture) so that passing a catheter through the cervix is very difficult or impossible. I have not (yet) found a cervix that is so scarred from surgery that I could not perform the HSG using an acorn tip catheter. Also, the catheter that is passed directly into the uterine cavity sometimes makes a groove in the endometrial lining (lining of the uterine cavity) that is then often seen on HSG (and can be difficult to distinguish from a more permanent irregularity of the cavity) and when the balloon is filled within the cavity it obscures the view of the cavity (you cannot see around the filling defect caused by the inflated balloon).
In general, I prefer the acorn tip catheter system. I especially prefer this system in women who have a cervix that might be difficult to canulate or a uterine cavity with (suspected) subtle lesions.
Case: 38 year old G0 with a history of regular menstrual intervals every 30-33 x 5 days with spotting (flow of a small amount of blood) from the vagina nearly daily. During the clinical evaluation, an ultrasound identified multiple uterine leiomyomata (fibroids) that were described as transmural (through the wall) and subserosal (on the outside surface). A hysterosalpingogram (HSG) is also suggested.
Question: If fertility is not an immediate issue for this woman, should she consider a HSG?
Answer: The cause of abnormal uterine bleeding should be investigated thoroughly.
The most common causes of vaginal bleeding in women of reproductive age are disorders of pregnancy. Systemic diseases (blood clotting abnormalities, liver disease), hormone imbalances (thyroid and prolactin) that can result in an ovulation dysfunction, malignancies of the reproductive tract (vulva, vagina, cervix, uterus), foreign bodies in the vagina or uterus, chronic inflammation of the endometrium or cervix, and local trauma should also be considered.
Uterine lesions that should be excluded include endometrial polyps, submucosal fibroids, chronic endometritis, and malignancy. An endometrial biopsy can diagnose chronic endometritis or malignancy. Endometrial polyps and submucosal fibroids are difficult to reliably see on transvaginal ultrasonography so further study should be considered. Sonohysterography, HSG, or hysteroscopy are commonly recommended for this purpose. I generally start with a HSG since I find the sensitivity (in my own hands) to be better than sonohysterography and it is less invasive than hysteroscopy.
If a filling defect within the uterine cavity is seen on HSG then I usually suggest that it be removed under direct visualization (via hysteroscopy). A dilatation and curettage (D+C) is a blind procedure where the uterine cavity is curetted (scraped) without actually seeing inside the uterus so the lesion causing the problem may be missed (left in place). Operative hysteroscopy is commonly available (USA) and allows the abnormalities in the uterus to be removed under direct visualization. If childbearing is compete then a discussion of a hysterectomy may also be appropriate, depending on the patient’s specific history and the nature of the findings at HSG.
Case: 40 year old G0 with a history of regular menstrual intervals every 28-31 x 4-6 days, a normal hormone evaluation (TSH and Prolactin concentration), an encouraging assessment of ovarian reserve (basal FSH and Estradiol concentration), a normal postcoital test, and a husband with unproven fertility (no prior pregnancy) yet a normal semen analysis. A hysterosalpingogram is performed and it reveals a normal appearing uterine cavity with bilateral proximal tubal occlusion.
Question: What should be considered in this situation?
Answer: When I find (bilateral) proximal tubal occlusion at the time of a HSG (during an infertility evaluation) I usually suggest proximal tubal catheterization. The proximal tubal catheterization should ideally be performed by someone with a lot of experience in the procedure since it can be long (30-45 minutes) and difficult (it requires patience). The radiologist that I generally use for my patients undergoing proximal tubal catheterization has a great deal of patience with the procedure and often takes a lot of time to complete the procedure properly. His success rate at opening the occluded tubes is consequently very good.
Proximal tubal catheterization often can accomplish the goal (opening the tubes) without resorting to more aggressive measures such as surgery.
Case: 29 year old G0 with a history of regular menstrual intervals every 27-28 x 5 days, a normal hormone evaluation (TSH and Prolactin concentration), a normal postcoital test, and a husband with unproven fertility (no prior pregnancy) yet a normal semen analysis. During a hysterosalpingogram (HSG) procedure the radioopaque dye was seen to intravasate into (enter into the blood vessels or lymphatics of) the uterine muscular wall.
Question: What should be done when intravasation of radioopaque dye is identified?
Answer: The radioopaque dyes that are used during HSGs may be water soluble or oil based.
I generally use water soluble dyes since I am pleased with the detail that is seen during the procedure and there is less potential for serious complications (significantly there is no risk of a potentially lethal oil embolus). The water soluble dye would normally flow into the uterine cavity, out through the fallopian tubes, and then it could be reabsorbed across the peritoneal lining of the pelvis and abdomen into the circulation. Excretion is then possible within the urine.
If I notice any direct intravasation of water soluble dye into the circulation via vessels in the muscular wall of the uterus then I immediately stop the procedure. On rare occasion, the HSG films will demonstrate the collection of a large amount of dye in the major veins of the pelvis after intravasation of dye. A small amount of intravasation is not known to be harmful if water soluble dye is used. I usually use a 10 mL or a 20 mL syringe containing 10 mL of dye to complete a HSG. I rarely need to use a 2nd 10 mL of radioopaque dye during a HSG.
Oil based dye is often thought to cause less cramping (uterine contractions) and may provide somewhat greater resolution so as to enhance the sensitivity of the test (increase the ability to identify very subtle details). My major concern with oil based dye is that if intravasation occurs and is not immediately recognized then this may result in the formation of granulomas or even a potentially fatal oil embolus. I avoid these oil based dyes for this reason (although I do recognize that there are many supporters of oil based dyes at many of the finest infertility programs in the USA).
Case: 32 year old G0 with a history of regular menstrual intervals every 29-31 x 3-5 days, a normal hormone evaluation (TSH and Prolactin concentration), a hysterosalpingogram revealing a normal uterine cavity and bilateral tubal patency, a normal postcoital test and a husband with unproven fertility (no prior pregnancy) yet a normal semen analysis.
Question: Should an endometrial biopsy be considered in this situation?
Answer: The role of an endometrial biopsy in an infertility evaluation is controversial. During an infertility evaluation a routine endometrial biopsy attempts to identify whether the lining cells of the uterine cavity (endometrium) are adequately prepared to allow for embryo implantation and the development of a normal pregnancy.
Many of the histologic (pertaining to the minute structure of tissues that requires a microscope to visualize) changes that occur during the menstrual cycle within the endometrium (that normally lines the uterine cavity) have been described. Other changes are currently under investigation.
Ideally, an endometrial biopsy would determine whether the uterine cavity is adequately “prepared” to allow for normal embryo implantation about a week following ovulation. Currently, this is not possible. However, the changes in an endometrial biopsy tissue that is obtained can be compared to the changes that are expected during “normal” development (as currently recognized and described) and when there is a “significant” lag in these changes then the test is considered to be abnormal.
If the dating of the obtained endometrial biopsy tissue (based on the histologic changes that are seen) reflects a greater than 2 day lag in development compared to “normal” (the expected appearance of the tissue for a comparable number of days after ovulation) then this is considered abnormal. An abnormal endometrial biopsy result suggests an insufficiency in (the biologic effect of) progesterone referred to as a luteal phase defect. Often the diagnosis of a luteal phase defect is not confirmed until 2 endometrial biopsies on consecutive menstrual cycles are found to be abnormal.
Case: 32 year old G0 with a history of regular menstrual intervals every 29-31 x 3-5 days, a normal hormone evaluation (TSH and Prolactin concentration), a hysterosalpingogram revealing a normal uterine cavity and bilateral tubal patency, a normal postcoital test and a husband with unproven fertility (no prior pregnancy) yet a normal semen analysis. An endometrial biopsy is performed and is found to be 3-4 days “out of phase.”
Question: What should be considered given this endometrial biopsy result?
Answer: A single endometrial biopsy that is found to be out of phase by 3-4 days (in a couple with no prior pregnancies) can be dealt with in a number of ways.
I would generally offer to repeat the endometrial biopsy on a subsequent cycle to confirm the presence of a persistent lag in development. In my experience women generally do not want the biopsy repeated since it can be a bit uncomfortable, is sometimes not covered by insurance (and can be expensive), and is often inconvenient since the day of ovulation during the biopsy cycle needs to be determined. If the endometrial biopsy is persistently abnormal or if there is one biopsy result that is abnormal (and the decision is made to not repeat the test) then I would consider the woman to have a “luteal phase defect.”
If I make the diagnosis of a luteal phase defect then I suggest treatment to enhance luteal phase progesterone concentration (such as clomiphene citrate or supplemental progesterone administration).
A luteal phase defect with a biopsy that is 3-4 days out of phase is more often associated with recurrent pregnancy loss than it is with infertility (ie., not getting pregnant). A lag in the endometrial biopsy result of 5 or more days is rarely seen and yet it is these tremendous lags in development that are more often associated with the inability to get pregnant. Therefore, some infertility specialists might not treat a luteal phase defect of 3-4 days unless there is a history of pregnancy losses.
Case: 36 year old G0 with a history of regular menstrual intervals every 29-31 x 3-5 days, a normal hormone evaluation (TSH and Prolactin concentration), an encouraging ovarian reserve (basal FSH and estradiol concentration), a hysterosalpingogram revealing a normal uterine cavity and bilateral tubal patency, a normal postcoital test and a husband with unproven fertility (no prior pregnancy) yet a normal semen analysis. An endometrial biopsy is performed during consecutive menstrual cycles and is found to be persistently 4-5 days “out of phase.”
Question: What treatment alternatives should be considered given these endometrial biopsy results?
Answer: Increasing the amount of progesterone that is produced by the ovaries or (exogenous) progesterone supplementation should be considered.
Clomiphene citrate is thought to effectively increase postovulatory progesterone production by the ovaries, especially if there is a history of irregular menstrual intervals or the ovarian follicles are smaller than usual at the time of ovulation.
When there is a history of either menstrual irregularity or long intermenstrual intervals and a luteal phase defect, I often suggest clomiphene citrate to regularize (or shorten) the cycles and (ideally) enhance progesterone production.
If there is no evidence of an ovulation dysfunction (by either intermenstrual interval regularity or length) then I would normally suggest supplemental progesterone administration as treatment for a luteal phase defect. If clomiphene citrate is still desired by the couple within this context, then prior to clomiphene treatment I would suggest obtaining an ultrasound of the ovaries immediately prior to ovulation to confirm that the lead (dominant) ovarian follicle is indeed small (generally less than 18mm in diameter at the time of ovulation to suggest that follicular size is the cause of the luteal phase defect). If the preovulatory dominant follicle is greater than 18mm in diameter and there is no other evidence of an ovulatory dysfunction, then I would encourage supplemental administration of progesterone rather than clomiphene citrate.
Natural progesterone can be administered orally, per vagina or as an intramuscular injection.
The oral form appears to be well tolerated by women and in my experience seems to be effective. I generally suggest 100mg micronized natural progesterone by mouth two or three times a day. If the endometrial biopsies are greater than 3 days out of phase I usually use the three times a day dosing. A repeat endometrial biopsy on progesterone is discussed and often suggested if there is a history of recurrent pregnancy loss or biopsies that are greater than 3 days out of phase.
The vaginal forms include both suppositories and a cream (crinone). The suppositories seem to melt when heated to body temperature and can become messy. The progesterone within crinone is suspended in a medium that does not change consistency when heated to body temperature so it tends to be well tolerated (one down side of crinone is that it can be much more expensive). I have generally had good results with the vaginal forms of progesterone.
Progesterone injections are in an oil base, which makes it necessary to use a relatively large bore needle and the oil does not tend to disperse very quickly. This form of progesterone is less well tolerated by women so I only use it routinely for my In Vitro Fertilization patients or if other forms of progesterone do not correct the endometrial biopsy adequately.