Ohjectiues: To evaluate, in women with postmenopausal bleeding, the effect of hormonal replacemen... more Ohjectiues: To evaluate, in women with postmenopausal bleeding, the effect of hormonal replacement (HRT) therapy on the endometrial thickness as measured by transvaginal sonography in relation to endometrial histology. Metho&: 1110 women with sequential/progestin treatment (E + P) (n = 202), with Estriol treatment (n = 149) or without HRT (n = 759) and postmenopausal bleeding were examined by transvaginal sonography (TVS) prior to curettage, with special reference to the relation of endometrial thickness to its histopathology. Results: The distribution of endometridl pathology was different in those women with E + P and Estriol compared with those without HRT. Endometrial pathology was found most frequently in women with an endometrium exceeding 8 mm in thickness. Furthermore, the incidence was found to increase with increasing endometrial thickness in all treatment groups. Atrophy was found significantly more often in women without HRT. Hormonal effects on the endometrium were found significantly more often in women with E + P and Estriol. Endometrial hyperplasia was found most commonly in women with Estriol in the thickness group 5-8 mm (P-C 0.001) as compared to those with HRT and without HRT. Endometrial cancer occurs most in women without HRT, in those women with an endometrium exceeding 8 mm in thickness as compared both to the E + P (P < 0.001) group and to the Estriol (P < 0.001) group. Endometrial cancer did not occur in any woman (with E + P, Estriol or without HRT) with an endometrial thickness of I 4 mm. Conclusions: TVS is of value for excluding endometrial pathology in women with HRT and postmenopausal bleeding. The distribution of endometrial findings and histopathological diagnosis in women with abnormal postmenopausal bleeding was different in women with E + P than in women without HRT. Furthermore, the cutoff for excluding endometrial abnormalities is the same in both groups i.e. < 4 mm.
To assess regional changes in ultrasound-derived indices of blood flow in the dominant human foll... more To assess regional changes in ultrasound-derived indices of blood flow in the dominant human follicle after the plasma LH surge. A cross-sectional, prospective study. Reproductive medicine unit at a university. Women attending an assisted conception clinic to determine the appropriate time to transfer previously frozen embryos during a natural cycle. Transvaginal ultrasonography with color Doppler imaging and pulsed Doppler spectral analysis was used to obtain indices of blood flow and velocity from vessels in the base, lateral part, and apex of the dominant follicle on days 10-12 (from day 1 of menses) and after the LH surge, but before rupture. Immunoassays were used to measure the blood concentrations of LH twice daily (at 8-10 A.M. and 4-6 P.M.) from cycle day 10. The pulsatility index (PI), resistance index (RI), peak systolic velocity (PSV), and time-averaged maximum velocity (TAMXV) in the uterine arteries and three regions of the dominant follicle (apical, lateral, and basal parts); follicular volume; the day and time of the onset of the LH surge (defined as first concentration of LH &gt; 22 U/L) and the times of each scan. Twenty-two women (aged 28-39 years) were studied and seven were scanned on days 10-12. A retrospective examination of the data from the remainder showed that eight were scanned &lt; 20 hours after onset of the LH surge and seven were scanned &gt; 20 hours after the onset of the LH surge. There was a significant increase in follicular volume after the LH surge. The PI was similar in vessels from the base (0.86 +/- 0.11; mean +/- SEM), lateral part (0.72 +/- 0.51) and apex (0.67 +/- 0.09) at cycle days 10-12 and then gradually decreased in the apex. There were similar changes in the RI. The PSV (mean +/- SEM; cm/s) was similar in vessels from the base (10.1 +/- 1.64), lateral side (8.2 +/- 1.43), and apex (9.2 +/- 1.91) in follicles of days 10-12. Within 20 hours of the onset of the LH surge, the PSV had increased in basal vessels (23.4 +/- 4.10), remained similar in lateral vessels (11.64 +/- 3.18), and was undetectable in apex vessels from six of eight follicles. Twenty hours after the LH surge, there was no pulsatile blood flow observed in the apical part of the follicle, but there was a sustained high PSV in the base (15.73 +/- 3.42) and lateral side (9.02 +/- 1.5). There were corresponding changes in the TAMXV. During the ovulatory process there are prominent changes in the regional blood flow of the follicle with a marked increase of the flow to the base of the follicle and a concomitant decrease of blood flow to the apex. These changes may be essential for the release of a mature oocyte.
BACKGROUND: Progestins as well as estrogens have a role in breast cell proliferation and the deve... more BACKGROUND: Progestins as well as estrogens have a role in breast cell proliferation and the development of breast cancer. Here, the effect of mifepristone on cell proliferation in human breast tissue in vivo was studied in premenopausal women. METHODS: A group of 30 women, scheduled for surgical treatment of leiomyomas, were randomized to either 50 mg mifepristone or placebo every other day, for 3 months. Fine needle aspiration biopsies were obtained at baseline and after 3 months. Immunocytochemical analysis of Ki-67 was performed to reflect breast epithelial cell proliferation. Samples from 14 women were included in the final analyses. RESULTS: The Ki-67 index was significantly reduced after mifepristone treatment compared with baseline (P 5 0.012). Furthermore, less individual variation in the Ki-67 index was seen in the mifepristone group. Treatment with mifepristone did not affect cortisol levels, whereas an increase in serum testosterone was noted. Breast symptoms like soreness and swelling were reduced, whereas the incidence of flushes increased. CONCLUSIONS: The ability of mifepristone to block breast epithelial cell proliferation in premenopausal women may prove beneficial when used for contraceptive purposes or for other gynaecological indications. Future studies should address a possible antiproliferative effect in the post-menopausal breast tissue during hormone replacement therapy. Our results implicate a possible protective effect of mifepristone on the breast epithelium. ClinicalTrials.gov NCT00579475.
The aim of the study reported here was to establish complementary data for changes in uterine siz... more The aim of the study reported here was to establish complementary data for changes in uterine size, echogenicity and vascularity during the menstrual cycle relative to a positive self-test for urinary luteinizing hormone (LH) and day 1 of next menses. Thirteen volunteers (aged 23-32 years) with apparently regular menstrual cycles were recruited from the nursing staff. The plan was to examine all women by transvaginal ultrasonography with colour Doppler imaging on day 11 of the menstrual cycle. A urinary LH self-test was to be used daily until a positive result was obtained and the women were to be re-scanned daily until the dominant follicle had ruptured. All women were then to be scanned at least every 48 h (within +/- 2 h of the same time of day) until day 6 of the next menstrual cycle. Matched samples of peripheral blood were taken at the time of each scan for hormone analysis. The main outcome measures were the times of follicular rupture, a positive test result for urinary LH and the start of menses, uterine volume, cavity length, endometrial thickness and grade, pulsatility index (PI), and time-averaged and peak systolic maximum velocities in uterine and radial arteries and in subendometrial vessels. Nine women fulfilled the criteria for an ovulatory cycle, and seven provided data over the complete study. The principal changes relative to a positive urinary LH test were (i) a continued rise in endometrial thickness to days 3 and 4 (this index then remained relatively constant, but the layered appearance was lost) and (ii) a gradual decrease in the uterine arterial PI. There was a significant rise in uterine volume, cavity length and uterine arterial PI around the time of the next menses, and a fall in endometrial thickness and blood velocity in the uterine and radial arteries and subendometrial vessels. The data may have implications for the assessment of reproductive status and the design of future studies on disorders of implantation or menstruation.
(+)421 mls] and the mean%error was 73% (SD + / − 210 mls, R (-)92-(+)1200 mls). DP tended to over... more (+)421 mls] and the mean%error was 73% (SD + / − 210 mls, R (-)92-(+)1200 mls). DP tended to over-estimate with smaller volumes but accuracy improved with larger volumes. There was no correlation between the%error and either abdominal girth or uterine size, although as the latter increased, the % error tended to increase as well (Pearson's r = 0.491, P < 0.001). Conclusions: We failed to validate the use of DP to estimate residual bladder volume in the early puerperium. Although CUS was comparable to UC, the latter remains the ''gold standard'', as the need for training limits routine CUS use by allied health professionals.
We compared the efficacy of conventional oral and transdermal HRT with that of tibolone, a synthe... more We compared the efficacy of conventional oral and transdermal HRT with that of tibolone, a synthetic steroid with mixed oestrogenic, ~drogenic and pro~estat~onal activity on prevention of bone Ioss at the whole skeleton, and at lumbar spine and hip. In an open, 'L-year study, 140 postmenopausal women (age 52*0.6years), were enrolled to either a control group (CO) or randomized to 1) tibolone (TIB), 2.5mg/day, 2) oral Ez (2mg/day) plus sequential oral dydrogesterone (DYD, lOmg/day for 14 days of a Z-day cycle), or 3) transdermal E2 (TTS) by patch releasing 5Oug/day. plus DYD as above. Bone densitometry of whole body (n=l1.5), lumbar spine and upper femur (n=l40) was performed using DXA technique (Hologic QDR IOOOW~ at baseline, and 6, 12, I8 and 24 months after initiation of therapy. Whole body bone mass (BMC, grams) increased (P<O.OOl) to a similar extent in all three treatment groups, i.e. by 2.4+0.5% in the TIB group, by 1.9&0.5% in the 'ITS group and by 1.5~0.5% in the oral Ez group. whereas it decreased by 1.6*0.5% (p<O.OOl) in non treated women.
To study the long-term effects of oral estriol tablets on the endometrium of postmenopausal women... more To study the long-term effects of oral estriol tablets on the endometrium of postmenopausal women by TVS and histology. This was a cross sectional, parallel-group, multicenter trial of 241 postmenopausal women, out of whom 125 were treated with oral estriol and 116 were untreated controls. Endometrial histology using Pipelle biopsies and/or dilatation and curettage (D&amp;C) was taken, endometrial thickness was assessed by use of transvaginal ultrasound (TVS), and the relation between endometrial thickness and histology was calculated. No statistically significant differences between the two groups were found in endometrial histology. There were found more polyps in the oral estriol group (14.0%) as compared with the control group (2.9%). The mean endometrial thickness in the oral estriol group was 3.0 mm compared with a mean value of 2.4 mm in the control group: P=0.01. No clinically relevant difference was found between the endometrium status (assessed by histology and TVS) of postmenopausal women on long-term oral estriol therapy and untreated controls. This trial supports the endometrial safety of maintenance treatment with oral estriol tablets. However, there are signs, not statistically significant, that may be associated with more endometrial polyps in postmenopausal women than if therapy is not given and that TVS is a useful instrument for the diagnosis.
To evaluate the effect of hormone replacement treatment (HRT) with percutaneous estradiol and cyc... more To evaluate the effect of hormone replacement treatment (HRT) with percutaneous estradiol and cyclical peroral medroxyprogesterone acetate (MPA) every month or every third month on the uterus and endometrium of postmenopausal women. Uterine size and endometrial thickness were measured by transvaginal sonography in 159 postmenopausal women before HRT, and after 6 and 12 months on HRT during 9-12 days of the MPA administration periods. During HRT, uterine size and endometrial thickness increased. The percentage increase in uterine diameter varied between 3.8% and 19.6%, and endometrial thickness varied between 28.7% and 76.4%, being greater in the group receiving MPA every third month than in the groups receiving MPA every month. Myomas grew during the first 6 months on HRT but increased no further during the next 6 months on HRT. The increases in uterine size, myomas and endometrial thickness during HRT were moderate and not problematic and occurred mainly during the first 6 months on HRT.
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2000
To compare the use a simplified ultrasound based infertility investigation of the infertile coupl... more To compare the use a simplified ultrasound based infertility investigation of the infertile couple with the current use of laparoscopy and hysteroscopy. Thirty-three infertile couples underwent transvaginal ultrasound and hystero-salpingo-contrast-sonography. A diagnosis was formulated based on the results of the ultrasound investigations, a semen analysis and endocrine parameters. The following day, all subjects underwent a laparoscopic chromotubation and hysteroscopy by a surgeon unaware of the ultrasound findings. A diagnosis based on the findings at laparoscopy and hysteroscopy, the same semen analysis and endocrine parameters, was then made. The two diagnoses were compared. A 90.9% agreement was found between the diagnoses made from the two methods used. When considering laparoscopic diagnosis the Gold Standard of tubal patency, the sensitivity to diagnose occluded tubes using hystero-contrast-sonography was 92.8%. The corresponding figures for specificity, PPV and NPV were 96.2%, 92.8% and 98.1%, respectively. A simple, ultrasound based approach to investigate the infertile couple, can be used effectively as an initial examination modality during the couple&#39;s work-up. However, there is a need for a larger study to confirm these results.
Ohjectiues: To evaluate, in women with postmenopausal bleeding, the effect of hormonal replacemen... more Ohjectiues: To evaluate, in women with postmenopausal bleeding, the effect of hormonal replacement (HRT) therapy on the endometrial thickness as measured by transvaginal sonography in relation to endometrial histology. Metho&: 1110 women with sequential/progestin treatment (E + P) (n = 202), with Estriol treatment (n = 149) or without HRT (n = 759) and postmenopausal bleeding were examined by transvaginal sonography (TVS) prior to curettage, with special reference to the relation of endometrial thickness to its histopathology. Results: The distribution of endometridl pathology was different in those women with E + P and Estriol compared with those without HRT. Endometrial pathology was found most frequently in women with an endometrium exceeding 8 mm in thickness. Furthermore, the incidence was found to increase with increasing endometrial thickness in all treatment groups. Atrophy was found significantly more often in women without HRT. Hormonal effects on the endometrium were found significantly more often in women with E + P and Estriol. Endometrial hyperplasia was found most commonly in women with Estriol in the thickness group 5-8 mm (P-C 0.001) as compared to those with HRT and without HRT. Endometrial cancer occurs most in women without HRT, in those women with an endometrium exceeding 8 mm in thickness as compared both to the E + P (P < 0.001) group and to the Estriol (P < 0.001) group. Endometrial cancer did not occur in any woman (with E + P, Estriol or without HRT) with an endometrial thickness of I 4 mm. Conclusions: TVS is of value for excluding endometrial pathology in women with HRT and postmenopausal bleeding. The distribution of endometrial findings and histopathological diagnosis in women with abnormal postmenopausal bleeding was different in women with E + P than in women without HRT. Furthermore, the cutoff for excluding endometrial abnormalities is the same in both groups i.e. < 4 mm.
To assess regional changes in ultrasound-derived indices of blood flow in the dominant human foll... more To assess regional changes in ultrasound-derived indices of blood flow in the dominant human follicle after the plasma LH surge. A cross-sectional, prospective study. Reproductive medicine unit at a university. Women attending an assisted conception clinic to determine the appropriate time to transfer previously frozen embryos during a natural cycle. Transvaginal ultrasonography with color Doppler imaging and pulsed Doppler spectral analysis was used to obtain indices of blood flow and velocity from vessels in the base, lateral part, and apex of the dominant follicle on days 10-12 (from day 1 of menses) and after the LH surge, but before rupture. Immunoassays were used to measure the blood concentrations of LH twice daily (at 8-10 A.M. and 4-6 P.M.) from cycle day 10. The pulsatility index (PI), resistance index (RI), peak systolic velocity (PSV), and time-averaged maximum velocity (TAMXV) in the uterine arteries and three regions of the dominant follicle (apical, lateral, and basal parts); follicular volume; the day and time of the onset of the LH surge (defined as first concentration of LH &gt; 22 U/L) and the times of each scan. Twenty-two women (aged 28-39 years) were studied and seven were scanned on days 10-12. A retrospective examination of the data from the remainder showed that eight were scanned &lt; 20 hours after onset of the LH surge and seven were scanned &gt; 20 hours after the onset of the LH surge. There was a significant increase in follicular volume after the LH surge. The PI was similar in vessels from the base (0.86 +/- 0.11; mean +/- SEM), lateral part (0.72 +/- 0.51) and apex (0.67 +/- 0.09) at cycle days 10-12 and then gradually decreased in the apex. There were similar changes in the RI. The PSV (mean +/- SEM; cm/s) was similar in vessels from the base (10.1 +/- 1.64), lateral side (8.2 +/- 1.43), and apex (9.2 +/- 1.91) in follicles of days 10-12. Within 20 hours of the onset of the LH surge, the PSV had increased in basal vessels (23.4 +/- 4.10), remained similar in lateral vessels (11.64 +/- 3.18), and was undetectable in apex vessels from six of eight follicles. Twenty hours after the LH surge, there was no pulsatile blood flow observed in the apical part of the follicle, but there was a sustained high PSV in the base (15.73 +/- 3.42) and lateral side (9.02 +/- 1.5). There were corresponding changes in the TAMXV. During the ovulatory process there are prominent changes in the regional blood flow of the follicle with a marked increase of the flow to the base of the follicle and a concomitant decrease of blood flow to the apex. These changes may be essential for the release of a mature oocyte.
BACKGROUND: Progestins as well as estrogens have a role in breast cell proliferation and the deve... more BACKGROUND: Progestins as well as estrogens have a role in breast cell proliferation and the development of breast cancer. Here, the effect of mifepristone on cell proliferation in human breast tissue in vivo was studied in premenopausal women. METHODS: A group of 30 women, scheduled for surgical treatment of leiomyomas, were randomized to either 50 mg mifepristone or placebo every other day, for 3 months. Fine needle aspiration biopsies were obtained at baseline and after 3 months. Immunocytochemical analysis of Ki-67 was performed to reflect breast epithelial cell proliferation. Samples from 14 women were included in the final analyses. RESULTS: The Ki-67 index was significantly reduced after mifepristone treatment compared with baseline (P 5 0.012). Furthermore, less individual variation in the Ki-67 index was seen in the mifepristone group. Treatment with mifepristone did not affect cortisol levels, whereas an increase in serum testosterone was noted. Breast symptoms like soreness and swelling were reduced, whereas the incidence of flushes increased. CONCLUSIONS: The ability of mifepristone to block breast epithelial cell proliferation in premenopausal women may prove beneficial when used for contraceptive purposes or for other gynaecological indications. Future studies should address a possible antiproliferative effect in the post-menopausal breast tissue during hormone replacement therapy. Our results implicate a possible protective effect of mifepristone on the breast epithelium. ClinicalTrials.gov NCT00579475.
The aim of the study reported here was to establish complementary data for changes in uterine siz... more The aim of the study reported here was to establish complementary data for changes in uterine size, echogenicity and vascularity during the menstrual cycle relative to a positive self-test for urinary luteinizing hormone (LH) and day 1 of next menses. Thirteen volunteers (aged 23-32 years) with apparently regular menstrual cycles were recruited from the nursing staff. The plan was to examine all women by transvaginal ultrasonography with colour Doppler imaging on day 11 of the menstrual cycle. A urinary LH self-test was to be used daily until a positive result was obtained and the women were to be re-scanned daily until the dominant follicle had ruptured. All women were then to be scanned at least every 48 h (within +/- 2 h of the same time of day) until day 6 of the next menstrual cycle. Matched samples of peripheral blood were taken at the time of each scan for hormone analysis. The main outcome measures were the times of follicular rupture, a positive test result for urinary LH and the start of menses, uterine volume, cavity length, endometrial thickness and grade, pulsatility index (PI), and time-averaged and peak systolic maximum velocities in uterine and radial arteries and in subendometrial vessels. Nine women fulfilled the criteria for an ovulatory cycle, and seven provided data over the complete study. The principal changes relative to a positive urinary LH test were (i) a continued rise in endometrial thickness to days 3 and 4 (this index then remained relatively constant, but the layered appearance was lost) and (ii) a gradual decrease in the uterine arterial PI. There was a significant rise in uterine volume, cavity length and uterine arterial PI around the time of the next menses, and a fall in endometrial thickness and blood velocity in the uterine and radial arteries and subendometrial vessels. The data may have implications for the assessment of reproductive status and the design of future studies on disorders of implantation or menstruation.
(+)421 mls] and the mean%error was 73% (SD + / − 210 mls, R (-)92-(+)1200 mls). DP tended to over... more (+)421 mls] and the mean%error was 73% (SD + / − 210 mls, R (-)92-(+)1200 mls). DP tended to over-estimate with smaller volumes but accuracy improved with larger volumes. There was no correlation between the%error and either abdominal girth or uterine size, although as the latter increased, the % error tended to increase as well (Pearson's r = 0.491, P < 0.001). Conclusions: We failed to validate the use of DP to estimate residual bladder volume in the early puerperium. Although CUS was comparable to UC, the latter remains the ''gold standard'', as the need for training limits routine CUS use by allied health professionals.
We compared the efficacy of conventional oral and transdermal HRT with that of tibolone, a synthe... more We compared the efficacy of conventional oral and transdermal HRT with that of tibolone, a synthetic steroid with mixed oestrogenic, ~drogenic and pro~estat~onal activity on prevention of bone Ioss at the whole skeleton, and at lumbar spine and hip. In an open, 'L-year study, 140 postmenopausal women (age 52*0.6years), were enrolled to either a control group (CO) or randomized to 1) tibolone (TIB), 2.5mg/day, 2) oral Ez (2mg/day) plus sequential oral dydrogesterone (DYD, lOmg/day for 14 days of a Z-day cycle), or 3) transdermal E2 (TTS) by patch releasing 5Oug/day. plus DYD as above. Bone densitometry of whole body (n=l1.5), lumbar spine and upper femur (n=l40) was performed using DXA technique (Hologic QDR IOOOW~ at baseline, and 6, 12, I8 and 24 months after initiation of therapy. Whole body bone mass (BMC, grams) increased (P<O.OOl) to a similar extent in all three treatment groups, i.e. by 2.4+0.5% in the TIB group, by 1.9&0.5% in the 'ITS group and by 1.5~0.5% in the oral Ez group. whereas it decreased by 1.6*0.5% (p<O.OOl) in non treated women.
To study the long-term effects of oral estriol tablets on the endometrium of postmenopausal women... more To study the long-term effects of oral estriol tablets on the endometrium of postmenopausal women by TVS and histology. This was a cross sectional, parallel-group, multicenter trial of 241 postmenopausal women, out of whom 125 were treated with oral estriol and 116 were untreated controls. Endometrial histology using Pipelle biopsies and/or dilatation and curettage (D&amp;C) was taken, endometrial thickness was assessed by use of transvaginal ultrasound (TVS), and the relation between endometrial thickness and histology was calculated. No statistically significant differences between the two groups were found in endometrial histology. There were found more polyps in the oral estriol group (14.0%) as compared with the control group (2.9%). The mean endometrial thickness in the oral estriol group was 3.0 mm compared with a mean value of 2.4 mm in the control group: P=0.01. No clinically relevant difference was found between the endometrium status (assessed by histology and TVS) of postmenopausal women on long-term oral estriol therapy and untreated controls. This trial supports the endometrial safety of maintenance treatment with oral estriol tablets. However, there are signs, not statistically significant, that may be associated with more endometrial polyps in postmenopausal women than if therapy is not given and that TVS is a useful instrument for the diagnosis.
To evaluate the effect of hormone replacement treatment (HRT) with percutaneous estradiol and cyc... more To evaluate the effect of hormone replacement treatment (HRT) with percutaneous estradiol and cyclical peroral medroxyprogesterone acetate (MPA) every month or every third month on the uterus and endometrium of postmenopausal women. Uterine size and endometrial thickness were measured by transvaginal sonography in 159 postmenopausal women before HRT, and after 6 and 12 months on HRT during 9-12 days of the MPA administration periods. During HRT, uterine size and endometrial thickness increased. The percentage increase in uterine diameter varied between 3.8% and 19.6%, and endometrial thickness varied between 28.7% and 76.4%, being greater in the group receiving MPA every third month than in the groups receiving MPA every month. Myomas grew during the first 6 months on HRT but increased no further during the next 6 months on HRT. The increases in uterine size, myomas and endometrial thickness during HRT were moderate and not problematic and occurred mainly during the first 6 months on HRT.
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2000
To compare the use a simplified ultrasound based infertility investigation of the infertile coupl... more To compare the use a simplified ultrasound based infertility investigation of the infertile couple with the current use of laparoscopy and hysteroscopy. Thirty-three infertile couples underwent transvaginal ultrasound and hystero-salpingo-contrast-sonography. A diagnosis was formulated based on the results of the ultrasound investigations, a semen analysis and endocrine parameters. The following day, all subjects underwent a laparoscopic chromotubation and hysteroscopy by a surgeon unaware of the ultrasound findings. A diagnosis based on the findings at laparoscopy and hysteroscopy, the same semen analysis and endocrine parameters, was then made. The two diagnoses were compared. A 90.9% agreement was found between the diagnoses made from the two methods used. When considering laparoscopic diagnosis the Gold Standard of tubal patency, the sensitivity to diagnose occluded tubes using hystero-contrast-sonography was 92.8%. The corresponding figures for specificity, PPV and NPV were 96.2%, 92.8% and 98.1%, respectively. A simple, ultrasound based approach to investigate the infertile couple, can be used effectively as an initial examination modality during the couple&#39;s work-up. However, there is a need for a larger study to confirm these results.
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Papers by Seth Granberg