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Uterus
Case: 30 year old G0 with a history of regular menstrual intervals every 26-27 x 3-5 days, a normal hormone evaluation (TSH and Prolactin concentration), basal body temperature (BBT) charting suggesting ovulation about 9-10 days prior to the onset of a subsequent menstrual flow, a hysterosalpingogram (HSG) revealing a normal uterine cavity and bilateral tubal patency, a normal postcoital test (PCT) and a husband with proven fertility (one pregnancy in a previous relationship) and a normal semen analysis. An endometrial biopsy is performed since the BBTs suggest a luteal phase defect (progesterone insufficiency problem) and the biopsy performed 10 days after ovulation (detected with LH kit and BBT, which were internally consistent) is read as post-ovulation day 4.
Question: What further testing or treatments should be considered in this situation?
Answer: Reportedly, a single endometrial biopsy performed in the luteal phase of the menstrual cycle may be found to be abnormal in a relatively high percentage of normally ovulating women. Endometrial biopsies are abnormal far less often during two consecutive menstrual cycles, so many infertility specialists suggest confirming a single abnormal result with a second biopsy on the next menstrual cycle.
If the endometrial biopsy is performed in the context of abnormal BBTs and each suggests a significant luteal phase defect then I do not necessarily perform a second endometrial biopsy for confirmation.
If a luteal phase defect is identified, then the role of this progesterone insufficiency syndrome on reproductive potential is controversial. If the reading of the endometrial biopsy suggests a lag of greater than 4-5 days from the expected result, then most of the available medical literature suggests this may cause “infertility” (by not allowing for embryo implantation). If the lag is less dramatic than this, then the luteal phase defect is more likely to be associated with recurrent pregnancy loss rather than a problem with getting pregnant (embryo implantation).
In this situation, I generally would consider progesterone supplementation (oral, vaginal or intramuscular injection) and possibly clomiphene citrate (if the dominant ovarian follicle in a subsequent menstrual cycle is found to be less than 18 mm diameter at the time of ovulation). I would also consider (encourage) a repeat endometrial biopsy on a treatment regimen to confirm adequate maturation of the lining.
Case: 23 year old G0 with a history of irregular menstrual intervals every 1-4 months, a normal hormone evaluation (TSH and Prolactin concentration), basal body temperature (BBT) charting suggesting anovulation, a hysterosalpingogram (HSG) revealing a normal uterine cavity and bilateral tubal patency, a normal postcoital test (PCT) and a husband with proven fertility (one pregnancy in a previous relationship) and a normal semen analysis. The patient fails ovulation induction with clomiphene citrate (at dosing up to 150mg x 5 days on cycle days 5-9) so a pelvic evaluation in preparation for menotropin controlled ovarian hyperstimulation is performed. At the time of hysteroscopy, small thin stalked polypoid structures and some broad based irregularities within the uterine cavity are easily removed with the use of a resectoscope loop electrode (without the use of cautery). Pathology reports benign endometrium on histology.
Question: What is the likely significance of these uterine irregularities in this situation?
Answer: The reproductive significance of subtle irregularities of the endometrium (the lining of the uterine cavity) that are too small to be seen on HSG but which can be identified at hysteroscopy (possibly small endometrial polyps or localized overgrowths of normal tissue) is controversial. The available medical literature addressing this issue is very scanty.
In general, I perform continuous flow hysteroscopy for each of my infertility patients undergoing pelvic evaluation so that I can identify and remove any irregularities within the uterine cavity. My understanding is that a uterine cavity will have optimal reproductive potential when it is free of any defects or irregularities. Therefore, any irregularity that I can see during hysteroscopy is removed (the cavity is “smoothed over”) using the resectoscope loop electrode (which rarely requires the use of cautery) so as to normalize the shape of the cavity. Anecdotally, in my experience this seems to enhance reproductive potential in some but not all situations. I usually submit this tissue for pathology evaluation (usually as “rule out polyp”) and the tissue is often read as either “endometrial polyp” or “benign endometrium.” On a rare occasion, pathology will identify atypical endometrial hyperplasia (a pre-cancerous lesion) and once I removed a “polyp” and pathology reported out endometrial carcinoma (a cancer of the lining of the uterus).
Case: 37 year old G0 with a history of regular menstrual intervals every 29 x 4-5 days, a normal hormone evaluation (TSH and Prolactin concentration), an encouraging ovarian reserve (based on basal FSH and estradiol concentrations), basal body temperature (BBT) charting suggesting ovulation about 13-14 days prior to the onset of a subsequent menstrual flow, a hysterosalpingogram (HSG) revealing a small rounded filling defect within the uterine cavity (measuring less than 1cm in diameter, thought be the radiologist to possibly signify an air bubble in the radiopaque dye) and bilateral tubal patency, a normal postcoital test (PCT) and a husband with proven fertility (three pregnancies in a previous relationship) and a normal semen analysis. An ultrasound demonstrates a normal uterine contour with no identified abnormality in the endometrial stripe.
Question: What further testing or treatments should be considered in this situation?
Answer: In this case, a pelvic evaluation is in order.
If one believes that the HSG finding of a rounded filling defect on the films is likely to be an endometrial polyp or submucosal myoma (fibroid) then an operative hysteroscopy should be planned to remove the abnormality. If one believes that the HSG finding of a filling defect may be just an air bubble in the radiopaque dye that is used (air bubbles certainly can have this appearance) then the couple has unexplained infertility after completion of the basic noninvasive tests and should have a pelvic evaluation as the next diagnostic step in the infertility evaluation (at which time the hysteroscopy can further assess the uterine cavity).
I try to perform all of the HSG examinations on my own patients since I like to see all of the available information from the study (and I often cause much less discomfort than some of the local radiologists). If there is a question of an air bubble in the liquid then the patient can be repositioned slightly (by raising a hip) to see if the “bubble floats upward” and more dye can be instilled to flush the bubbles out the fallopian tubes. If there is a persistent nonmotile rounded filling defect in the uterine cavity then this is an abnormality (most likely polyp or fibroid).
Radiologists will sometimes suggest that a rounded filling defect (that is not a bubble) that is seen during the HSG examination may be too little to be clinically significant. This most often seems to come from their point of view that they are looking for “premalignant” lesions or obstructing lesions. From an infertility point of view, I think that any lesion (filling defect) that is consistently identified on HSG (which is a relatively insensitive test to start with) is large enough to possibly have a detrimental effect on embryo implantation. That is, a 1 cm diameter polyp or fibroid is many orders of magnitude larger than a human egg, sperm or embryo (fertilized egg) since a preimplantation embryo is microscopic in size (a human egg, sperm or embryo requires a microscope to be seen and can not be seen directly with the eye). The presence of these small filling defects within the uterine cavity may also act like IUDs (intrauterine devices) in that they may cause a failure of implantation simply due to their presence within the uterine cavity (and any local tissue reaction that may result from this).
Ultrasonography is relatively insensitive at identifying intrauterine filling defects (such as endometrial polyps or submucosal myomas) unless the cavity is filled with a liquid (such as sterile saline) for sonohysterography. Therefore, the inability to confirm the presence of a defect within the uterine cavity based on a transvaginal ultrasound exam does not contradict the finding of a defect in the cavity on HSG.
If a defect were seen within the uterine cavity at the time of hysteroscopy, I would generally remove it (regardless of its size) so as to optimize reproductive potential.
Case: 33 year old G0 with a history of regular menstrual intervals every 26 x 3 days, a normal hormone evaluation (TSH and Prolactin concentration), basal body temperature (BBT) charting suggesting ovulation about 14 days prior to the onset of a subsequent menstrual flow, a hysterosalpingogram (HSG) revealing an abnormal uterine cavity with multiple filling defects (ranging from less than 1cm to 2 cm diameter) and bilateral tubal patency, a normal postcoital test (PCT) and a husband with unproven fertility yet a normal semen analysis. Ultrasound examination reveals multiple defects within the uterine wall (most likely representing transmural fibroids) and a somewhat thickened endometrial stripe (12mm).
Question: What further testing or treatments should be considered in this situation?
Answer: A pelvic evaluation with operative hysteroscopy is in order.
If the presence of filling defects within the uterine cavity is confirmed at hysteroscopy then generally they should be removed. Fibroids can be partially submucosal and partially transmural where the relative percentage of the fibroid that enters the uterine cavity varies. Fibroids are composed of smooth muscle cells and are significantly “tougher” (firmer) tissue masses than endometrial polyps (which are composed of delicate epithelium called endometrium).
If the filling defects are submucosal leiomyomata (fibroids) then removal with a resectoscope loop electrode usually requires the concurrent use of monopolar cautery. Submucosal fibroids that are almost exclusively within the uterine cavity can generally be removed easily under direct visualization by transecting the small amount of tissue at the site of connection. Fibroids that are predominantly transmural (or have a significant transmural component) can be “shaved down” so that the uterine wall is smooth (does not have the fibroid projecting into the cavity).
When electrosurgical hysteroscopy is performed to remove tissue from within the uterus I usually suggest high dose intraoperative and postoperative estrogen (premarin 25mg IV intraoperatively and premarin 1.25mg to 2.5mg by mouth per day x 1-2 months with progesterone withdrawal flows) to promote growth of the endometrial lining over the “bald spots” in the lining (endometrium of the uterine cavity) that were caused by the procedure.
As always, caution (by the surgeon and operating room team) is required since the fibroid may be “fed” by a few large bore vessels within the “stalk” (connecting pedicle) such that a significant volume of hysteroscopic distending fluid may rapidly enter the transected vessels (since the uterus is distended to allow for visualization using this fluid under pressure during continuous flow hysteroscopy).
I usually do not remove fibroids that are transmural or subserosal (projecting into the pelvis from the outside of the uterus) since they rarely are known to affect reproductive potential. One exception is when there is a well demonstrated history of recurrent pregnancy loss that is entirely unexplained following a full evaluation (including all clinically valuable tests)-- in this case the potential benefits of removing the transmural fibroids may outweigh the surgical risks. Prior to this surgery there should be a full discussion (with the patient or couple) of the involved surgery and the fact that there is very little information (in the available medical literature) correlating reproductive performance and transmural myomas.
Case: 26 year old G3 S3 (three prior spontaneous pregnancy losses each completed with a D+C without apparent complication) with a history of regular menstrual intervals every 26-27 x 3-5 days, a normal hormone evaluation (TSH and Prolactin concentration), basal body temperature (BBT) charting suggesting ovulation about 12-14 days prior to the onset of a subsequent menstrual flow, a hysterosalpingogram (HSG) revealing an abnormal uterine cavity with multiple thin and thick linear filling defects suggestive of adhesions (synechiae) and bilateral tubal patency, a normal postcoital test (PCT) and a husband with proven fertility (three pregnancies with the patient) and a normal semen analysis.
Question: What further testing or treatments should be considered in this situation?
Answer: The HSG findings are very suggestive of Asherman’s syndrome (intrauterine adhesions or synechiae). The presence of scar tissue within the uterine cavity can result in recurrent pregnancy loss or the inability to become pregnant.
Operative hysteroscopy with removal of scar tissue from within the uterine cavity is indicated for Asherman’s syndrome.
Thin intrauterine adhesions are usually lysed relatively easily with a resectoscope loop electrode or other operative hysteroscopy tools (such as scissors through an operating port). The thicker adhesions are often more difficult to lyse, may have a greater muscular component (than thin adhesions), the vascular supply to the muscular component (of thick intrauterine adhesions) more often involves larger blood vessels, and therefore infusion of the distending medium into the transected larger bore vascular channels can be rapid.
Case: 34 year old G2 S2 (spontaneous pregnancy losses at 8 weeks gestation and 10 weeks gestation following ultrasound visualization of a fetal heart beat) with a history of regular menstrual intervals every 26-27 x 3-5 days, a normal hormone evaluation (TSH and Prolactin concentration), an encouraging ovarian reserve (basal FSH and estradiol concentrations), basal body temperature (BBT) charting suggesting ovulation about 13 days prior to the onset of a subsequent menstrual flow, a hysterosalpingogram (HSG) revealing an abnormal uterine cavity with a wedge shaped fundal defect (consistent with either a uterine septum or bicornuate uterus) and bilateral tubal patency, a normal postcoital test (PCT) and a husband with proven fertility (two pregnancies with the patient) and a normal semen analysis. A recurrent pregnancy loss evaluation (including an endometrial biopsy, chromosome analysis for both husband and wife, review of systems (history) to identify debilitating maternal diseases or exposure to environmental (embryo-) toxins, and bloodwork for immunologic causes of pregnancy loss) is performed and found to be otherwise normal.
Question: What further testing or treatments should be considered in this situation?
Answer: In this situation, I generally proceed with pelvic evaluation to define whether the wedge shaped defect in the uterine cavity is a uterine septum (which should be transected hysteroscopically) or a bicornuate uterus (where surgical repair requires a laparotomy with uterine reunification procedure).
The risk to benefit ratio for surgical repair of a bicornuate uterus in the face of otherwise “unexplained” pregnancy losses remains controversial. If the couple decides that they want to undergo the reunification surgery for a bicornuate uterus (if identified at pelvic evaluation) after a discussion of the (most current) available literature, risks, benefits, and alternatives then I would generally be willing to perform this surgery for them.
Preoperatively, the couple and I would review whether they want to proceed to laparotomy and uterine reunification at the time of the initial pelvic evaluation or whether they would prefer to reschedule this case (which would require a several week recovery period as opposed to a few day recovery period) if a bicornuate uterus is identified (to better plan their personal schedules).
In cases such as this one, I seem to find a uterine septum far more often than a bicornuate uterus. The hysteroscopic transection of a uterine septum is usually simple and straighforward with a resectoscope loop electrode and monopolar cautery (usually 50 W coagulation and 50 W cutting on blend 1). I generally give premarin to promote endometrial growth over the denuded regions of the uterine cavity (25mg IV intraoperatively and 2.5mg by mouth per day x 1-2 months with provera withdrawal flows) following transection.
Case: 37 year old G0 with a history of regular menstrual intervals every 26-27 x 7-8 days, a normal hormone evaluation (TSH and Prolactin concentration), an encouraging ovarian reserve (basal FSH and estradiol concentrations), severe dysmenorrhea (pain with menses) described “as if someone was stabbing me through the vagina into my uterus,” a hysterosalpingogram (HSG) revealing a normal uterine cavity and bilateral tubal patency, a normal postcoital test (PCT) and a husband with proven fertility (one pregnancy in a previous relationship) and a normal semen analysis. At pelvic evaluation a large (uniformly bulky and boggy) uterus is identified along with moderate pelvic endometriosis.
Question: What further testing or treatments should be considered in this situation?
Answer: Adenomyosis is a condition in which the endometrial tissue that normally lines the uterine cavity invades into the muscular wall of the uterus (on microscopic exam the endometrial glands or stroma are more than 2.5 mm below the basalis layer of the endometrium).
Many women with adenomyosis are asymptomatic (have no symptoms or complaints) or have minor nonspecific symptoms. Symptoms are more common after the age of 35 (until menopause) and most often seem to involve heavy menstrual flows and pain with menses (dysmenorrhea). The pain with menses is often described as a knife like sharp stabbing pain through the midline of the pelvis. Adenomyosis is reportedly found coincidentally with endometriosis about 25% of the time, which suggests that they are not strongly associated with one another. The uterus afflicted with adenomyosis is often boggy (soft) and uniformly enlarged (about 2 times normal size). Diagnosis is by microscopic examination of biopsy tissue (often at the time of hysterectomy).
Adenomyosis may reduce reproductive potential but the association between adenomyosis and subfertility is very poorly understood. Part of the problem in assessing a correlation between adenomyosis and infertility is the relative inability to accurately diagnose adenomyosis without deep tissue biopsies of the uterus (which in my experience are just not performed in order to make this diagnosis). Treatment of adenomyosis in a woman desiring fertility is also controversial since (to my knowledge) no treatment regimens have been shown to be effective (in the available medical literature). Hysterectomy is effective definitive treatment once childbearing is complete. The endometrial tissue that composes the adenomyosis has been reported to have no progesterone receptors and a reduced number of estrogen receptors so hormonal treatment of adenomyosis (which is often tried due to an absence of other reasonable alternatives) may be ineffective.
In this (presented) case, I would generally suggest aggressive treatment of all visible endometriosis and sampling of the endometrial cavity (to rule out other pathology). Hopefully at least part of the pain with menses will be relieved and the fertility enhanced by the treatment of the visible endometriosis. Further fertility care would otherwise not be altered due to the possibility of adenomyosis.
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