A phase II trial of thalidomide in patients with refractory uterine carcinosarcoma and correlation with biomarkers of angiogenesis: A Gynecologic Oncology Group study

Objectives

To evaluate the efficacy and adverse events of thalidomide in previously-treated, measurable, persistent or recurrent carcinosarcoma of the uterus, and to explore associations between angiogenic markers with patient demographics and clinical outcome.

Methods

Eligible, consenting patients were treated until disease progression or toxicity intervened with daily starting dose of 200 mg thalidomide/day that was increased by 200 mg every 2 weeks to a target dose of 1000 mg/day. Endpoints included progression-free survival (PFS) ≥ 6 months (primary), toxicity, response, overall PFS and survival. Pre- and post-treatment plasma were evaluated for a panel of angiogenic biomarkers and assessed against clinical outcomes.

Results

Of 55 enrolled patients, 45 were evaluable for toxicity and survival. Two patients (4%; 90% CI 1-13%) experienced a partial response, and 8 (18%; 90% CI 9-30%) had PFS ≥ 6 months. Median PFS was 1.9 months and median survival was 5.9 months. Grade 2-3 sensory neuropathy was noted in 6 patients, and 4, 3, and 3 patients experienced grade 3 sedation, fatigue, and constipation, respectively. Three patients had grade 4 adverse events (2 thromboembolic, 1 anemia). High pre-treatment VEGFA levels were associated with poorer PFS and survival.

Conclusions

Treatment with thalidomide met the protocol specified goal of prolonging PFS at 6 months. However, based on results with newer agents, the activity was insufficient to support further investigation. Association between pre-treatment VEGFA and prognosis in this population supports further evaluation of anti-angiogenic therapies in uterine carcinosarcoma.     

Fertility and obstetric outcome after conservative management of placenta accreta

Objective

To determine the fertility and obstetric outcomes after conservative management of placenta accreta.

Methods

A retrospective observational cohort study of all identified cases of placenta accreta from 1993 to 2007 in 2 tertiary university hospitals in France. For patients treated conservatively, maternal and fetal morbidity, reproductive function, fertility, and subsequent pregnancies were recorded.

Results

During the study period, 46 patients were treated by conservative management; 6 patients underwent a secondary hysterectomy. Of the remaining 40 patients, 35 were followed up for a median of 65 months (range 18-156 months). Patients resumed their menstrual cycles after a median of 130 days (range 48-176 days). Menses were irregular in 11 patients (31%), but none had amenorrhea. Twelve of the 14 patients desiring another pregnancy achieved a total of 15 pregnancies; 2 patients had recurrent placenta accreta. Five spontaneous abortions and 1 termination of pregnancy occurred during the first trimester. The median term at delivery was 37 weeks (range, 35-40 weeks). Four patients delivered prematurely.

Conclusion

Conservative management of placenta accreta can preserve fertility, although the risk of recurrent placenta accreta appears to be high.     

Caesarean section greatly increases risk of scar endometriosis

Objective

To estimate the incidence of scar endometriosis after different surgical procedures.

Study design

A retrospective study of 72 patients diagnosed with scar endometriosis between 1978 and 2003 was performed. Patient age, site of endometriosis, previous operations, time-gap between last surgery and onset of symptoms, nodule characteristics, and recurrence were evaluated.

Results

Age ranged from 16 to 48 years. Location varied according to the previous surgery: 46 caesarean section, one hysterectomy, one in abdominal surgery, 19 episiotomy, one was a relapse and two pelvic floor procedures, two women with no previous surgery. The incidence of scar endometriosis after caesarean section was significantly higher than after episiotomy (0.2 and 0.06%, respectively: p < 0.00001) with a relative risk of 3.3. Pain was the most frequent symptom. The mean time between surgery and onset of symptoms was 3.7 years.

Conclusion

Our findings confirm that scar endometriosis is a rare condition and indicate, probably for the first time, that caesarean section greatly increases the risk of developing scar endometriosis.     

Effect of age and stage of endometriosis on ovarian follicular loss during laparoscopic cystectomy for endometrioma

Objective

To identify the risk factors associated with inadvertent follicular loss during laparoscopic cystectomy for endometrioma.

Methods

Between April 2008 and April 2010, 114 patients who underwent laparoscopic cystectomy for endometrioma were enrolled in the study. Clinical data were collected, together with a retrospective review of medical records. Ovarian follicular loss and the thickness of the cystic wall removed were evaluated by pathologic slide review.

Results

Ovarian follicular loss was more frequently observed among younger patients (P < 0.001) and those with stage 3 endometriosis than among those with stage 4 (P = 0.027), in addition to having an inverse correlation with age (P < 0.001). The thickness of the removed ovarian tissue correlated with inadvertent follicular loss (P < 0.001); however, there was no correlation between any clinical parameter tested and the thickness of the removed ovarian tissue. There was a correlation between ovarian follicular loss and the thickness of the removed ovarian tissue among patients younger than 40 years (P < 0.001), but not among patients aged 40 years or older (P = 0.123).

Conclusion

Ovarian follicular loss was more common among younger patients and patients with lower-stage endometriosis. The thickness of the removed ovarian tissue did not differ among patients, despite varying clinical factors.     

The value of serological markers in the diagnosis and prognosis of endometriosis: a prospective case-control study

Objective

We analyzed selected well-known and less well-known serum markers that have been proposed for diagnosis and severity assessment of endometriosis, in a case-control study.

Study design

This prospective study was carried out in a Clinical Department of Gynecology in Iasi, Romania. Study participants included endometriosis patients, and controls in whom laparoscopy had excluded endometriosis. Each case and control was investigated for serum levels of CA125, TNF, IL-1, IL-6 and IL-8. The data were correlated with clinical symptoms and revised American Fertility Society (rAFS) score and stage, and interpreted by Mann-Whitney U-test and ANOVA regression analysis.

Results

Over the course of 1 year, 24 cases of endometriosis and 24 controls of matched age were selected. The rAFS stages were: stage I, 12.5%; stage II, 16.7%; stage III, 58.3%; and stage IV, 12.5%. CA125 levels were over the cut-off of 35 IU/l in 54% of patients (versus 8% of controls), averaging 67.5 (CI95: ±17.5). The sensitivity and specificity were 54% and 91%, respectively, with a p value of <0.001 (statistically significant). For IL-6, 71% of cases and 87% of controls were above the cut-off of 2 pg/ml, with an average of 11.83 ± 7. The sensitivity and specificity were 71% and 12%, respectively, but the difference was not statistically significant, p = 0.071. Other tested serum markers had no discrimination value. A correlation with severity of endometriosis was seen for CA125 (p = 0.03) but not for IL-6, by ANOVA.

Conclusion

CA125 correlated with endometriosis screening and severity, indicating its superiority as a marker for further, larger studies.     

Adenomyosis and junctional zone changes in patients with endometriosis

Objectives

To evaluate image findings in the junctional zone (JZ) in patients with endometriosis and correlate with image findings of adenomyosis. To attempt a correlation of the degree of adenomyotic infiltration with the degree of infiltration and stage of endometriosis.

Study design

Magnetic resonance imaging (MRI) of the uterus was performed in 153 women with suspected deeply infiltrating endometriosis and planned surgery, and in a reference group of 129 women without endometriosis, verified during hysterectomy. Changes in the JZ and endometriosis in the pelvis were described in detail. Diagnosis of adenomyosis at MRI was based on optimal criteria derived from the hysterectomy control group. The stage of endometriosis (AFS stage) was determined during surgery.

Results

In the group of women with endometriosis 34.6% had adenomyosis compared with 19.4% in the reference group (p < 0.05). More women with endometriosis (39.9%) had an irregular JZ compared to 22.5% in the reference group (p < 0.01). Among women with severe endometriosis (AFS stage IV) 42.8% had adenomyosis compared to 29.4% in the women with other stages of endometriosis (AFS stages I + II + III) (p = 0.10). More women with severe endometriosis (AFS stage IV) had deeper wall invasion of adenomyosis (p > 0.05) but the presence of deep infiltrative rectovaginal endometriosis and the size of infiltration were not correlated to adenomyosis or depth of infiltration of adenomyosis.

Conclusions

In a group of young women with severe symptomatic endometriosis and planned surgery a systematic evaluation of the JZ revealed that one third had uterine adenomyosis, but the invasive potential of endometrial cells in the uterus and in the peritoneum corresponded only to a limited degree.     

Timing of fertility preservation procedures in a cohort of female patients with cancer

Objective

Comparison of time intervals from diagnosis to chemotherapy between patients opting for embryo cryopreservation or ovarian tissue cryopreservation.

Study design

Retrospective analysis.

Setting

University hospital in the Netherlands.

Patients and methods

Thirty-five female patients undergoing fertility preservation procedures before treatment with chemotherapy for cancer. Embryo cryopreservation was performed in 12 patients and ovarian tissue cryopreservation in 23 patients. We investigated differences in time intervals (from diagnosis to start of chemotherapy) between patients opting for embryo cryopreservation and patients opting for ovarian tissue cryopreservation. We calculated time intervals between the moment of diagnosis, the moment of referral, the moment of consultation, the moment of finishing of the fertility preservation procedure and the start of chemotherapy.

Results

The median time between diagnosis and referral (median = 18 days) and between referral and consultation (median = 5 days) was comparable in both groups. A significant difference was found between ovarian tissue cryopreservation and embryo cryopreservation for the time interval between consultation and cryopreservation (p = 0.001). Ovarian tissue cryopreservation was completed for half of the patients within 6 days after consultation with the gynecologist, and the hormonal stimulation for embryo cryopreservation was completed for all patients within four weeks (median = 18 days), with a median of 11 days of hormonal stimulation. A significant difference was found between ovarian tissue cryopreservation and embryo cryopreservation in the time interval between fertility preservation and start of chemotherapy (median = 7 vs 19 days, p = 0.019). In sum, the total duration between diagnosis and chemotherapy was significantly shorter for ovarian tissue cryopreservation patients than for embryo cryopreservation patients (median = 47 vs 69 days, p = 0.042).

Conclusion

Embryo cryopreservation can be performed within the standard timeframe of cancer care in patients with breast cancer receiving adjuvant chemotherapy, but if delay of the start of chemotherapy is harmful, ovarian tissue cryopreservation can be done within one week.     

Do patients manage to achieve pregnancy after a major complication of deeply infiltrating endometriosis resection?

Objective

To evaluate the fertility status in women suffering from major postoperative complications following deep endometriosis surgery.

Study design

A retrospective study in teaching and research hospitals (tertiary centers) including 23 women submitted to the surgical treatment for deep endometriosis and presenting a major postoperative complication. Postoperatively, women desiring pregnancy who conceived were compared to those who did not conceive using Mann-Whitney test and Fisher's exact test. Main outcome measure included the pregnancy rate among these women.

Results

The overall intrauterine pregnancy rate was 47.8% and the live birth rate was 30.4%. There were 10 spontaneous conceptions and 3 IVF conceptions among 11 patients. Women who did not conceive were older than those who conceived (33.9 vs. 29.3 years; p = 0.02). The pregnancy rate after intestinal complications was lower than after urinary complications (33.3% vs. 83.3%; p = 0.04).

Conclusion

Fertility remains preserved among women experiencing a major complication after removal of deep endometriosis with a live birth rate of 30.4%. Women experiencing bowel complications have a reduced probability of conception compared with those who experience a urologic complication.     

Synchronous early-stage endometrial and ovarian cancer

Objective

To explore the clinicopathologic findings and oncological outcome of early-stage synchronous endometrial and ovarian malignancies.

Methods

A retrospective study of 93 women with synchronous stage I ovarian and stage I-II endometrial cancer treated between December 1981 and August 2005 in the gynecologic oncology department of San Gerardo Hospital, Italy.

Results

Fifty-one percent of the ovarian tumors were stage Ia and 71% of the endometrial cancers had minimal myometrial invasion. Endometrioid histology and grade 2 disease were prevalent in both sites. Hyperplasia and endometriosis coexisted in 71% and 22% of endometrial and ovarian cancers, respectively. The actuarial 5-year disease-free and overall survival rates were 83% and 96%, respectively.

Conclusion

The incidence of synchronous endometrial and ovarian cancer is not negligible, especially among young women. Synchronous cancers show very favorable pathologic features and have an excellent oncologic outcome. Adjuvant therapy should be tailored according to surgical staging and histology.     

Is acupuncture in addition to conventional medicine effective as pain treatment for endometriosis?: A randomised controlled cross-over trial

Objective

The aim of the study was to examine whether acupuncture is an effective additional pain treatment for endometriosis.

Study design

One hundred and one women aged 20-40 years participated and were randomised into two groups, each receiving two units of 10 acupuncture treatments, twice a week over a period of five weeks. Group 1 (n = 47) received verum-acupuncture during the first series, and group 2 (n = 54) received non-specific acupuncture. After the first unit of 10 treatments, an observation period of at least two menstruation cycles was set, followed by a second unit, according to a cross-over design. Prior to the study (during a two-week run-in period) the patients’ actual pain intensity was surveyed. Throughout the study period, participants were asked to keep a ‘pain protocol’, in which they defined and recorded their pain according to the 10-point visual analogue scale (VAS).

Results

Eighty-three out of a total of 101 patients finished the study. Group 1 showed a significant reduction of pain intensity after the first 10 treatments. In comparison, group 2 showed significant pain relief only after the cross-over.

Conclusion

Acupuncture treatment on specific acupuncture points appears to be an effective pain treatment for endometriosis, but this has to be confirmed in further study.     

Establishing the accuracy and acceptability of abdominal ultrasound to define the foetal head position in the second stage of labour: a validation study

Background

Deep infiltrating endometriosis (DIE) is associated with severe painful symptoms and represents a complex management challenge.

Objective

To analyse the effect of pregnancy on deep infiltrating lesions and related symptomatology.

Study design

As part of a longitudinal study performed over the past 3 years to determine the efficacy of hormonal treatment in treating women with DIE, we identified three cases of advanced pelvic endometriosis, all with DIE (deep recto-vaginal and recto-sigmoid involvement) where patients achieved spontaneous pregnancies. They were followed up by transvaginal ultrasound (TV-US). The main outcome measures were analysis of the size and echographic pattern of deep infiltrating lesions of endometriosis and evaluation of clinical symptoms during pregnancy.

Results

We observed modifications in lesion size and pattern. In the two patients observed in the third trimester, the lesions were more homogeneous with less evident limits of nodules and band-like echoes, less fibrotic-like. All patients showed complete resolution of symptoms during pregnancy.

Conclusions

The hormonal environment produced by pregnancy might determine significant modifications of endometriotic lesions and reduce painful symptoms. As surgery for DIE is difficult, complex and can lead to major complications, the achievement of a pregnancy-specific hormonal state, through pregnancy or hormonal treatment, may be a valid option in selected cases.     

Carbetocina vs. oxitocina para la prevención de hemorragia posparto en pacientes grandes multíparas: estudio aleatorizado controlado

Objective

Carbetocin is a long-acting oxytocin analogue that can be used as a uterotonic agent in the management of postpartum hemorrhage. The purpose of this study was to compare the effectiveness of carbetocin (100 μg IV) with that of oxytocin (20 U IV) in the prevention of postpartum bleeding in grand multiparous patients (five or more pregnancies).

Design

Prospective, randomized controlled trial.

Population

Patients with vaginal deliveries of singleton pregnancies (≥28 weeks).

Methods

A total of 135 patients were selected to receive 100 μg of carbetocin in a single IV dose or 400 mU oxytocin/min (LR 1000 cc+20 U oxytocin, 100 cc/h) at the end of the third stage of labor.Main outcome measures: Postpartum hemorrhage despite the medication used, requiring the use of alternative measures.

Results

There were no statistically significant differences in the frequency of therapeutic failures or the need to transfuse blood products. The use of carbetocin was associated with a lesser need to manually explore the uterus (RR: 0.12; 95% CL 0.03-0.48). The incidence of adverse effects was similar in both groups. There were no differences in the effects of drugs on breastfeeding.

Conclusions

The use of a single IV dose of carbetocin is as effective as 20 IV units of oxytocin in the prevention of postpartum hemorrhage in grand multiparous women after vaginal delivery. The incidence of adverse effects and complications was similar in the two groups. Carbetocin should be considered a useful alternative to conventional uterotonics in the prevention of postpartum bleeding in grand multiparous patients.     

Transretropubic traction vaginoplasty for correction of vaginal aplasia

Objective

To introduce an alternative approach to vaginoplasty using transretropubic traction (TRT).

Methods

In this case series with 4 patients with complete vaginal aplasia, a plastic “olive” placed on the vaginal dimple was lifted by a mesh tape inserted through the space of Retzius and anchored to the anterior abdominal wall.

Results

On day 8 postoperatively all patients had a reasonable vaginal size, 2.5 to 3 cm in width and 6 to 7.5 cm in length. The mean satisfaction scores were 86 points for the patients and 89 points for their husbands, who also reported a mean penetration score of 90 points.

Conclusion

As a minimal-access and relatively simple operation, TRT vaginoplasty could be performed by trained gynecologists. Studies with larger populations are required to support this preliminary report.     

The impact of anesthesia and mode of delivery on the urinary bladder in the postdelivery period

Objective

To evaluate the effect of regional anesthesia and mode of delivery on the function of the urinary bladder. The primary outcome was the time taken for urinary bladder sensation to return following various modes of delivery and analgesia/anesthesia. The secondary outcome was the volume of urine present in the bladder when sensation returned.

Methods

The study was conducted at the Birmingham Women's Foundation Trust, Birmingham, UK. A total of 120 postnatal patients were studied between January 2007 and March 2008. The volume of urine in the bladder when sensation first returned was measured by release of a clamp for women fitted with an indwelling catheter, and/or estimated using ultrasound.

Results

The median times for sensation to return to the bladder in patients who had a vaginal delivery without epidural analgesia, vaginal delivery with epidural analgesia, and after elective cesarean delivery under spinal anesthesia were 122 minutes (IQR, 112-136 minutes), 234 minutes (IQR, 202-291 minutes), and 374 minutes (IQR, 311-425 minutes), respectively. The median urine volumes were 144 mL (IQR, 112-192 mL), 200 mL (IQR, 136-336 mL), and 152.5 mL (IQR, 125-270 mL), respectively.

Conclusion

These results should be taken into consideration when formulating a postdelivery bladder care protocol.     

Luteinizing hormone β-subunit gene (LHβ) polymorphism in infertility and endometriosis-associated infertility

Objective

To establish the frequency of LHβ G1502A polymorphism in infertile women with endometriosis, infertile women without endometriosis and a control group.

Study design

Case-control study including 110 infertile women with endometriosis, 84 infertile women without endometriosis and a control group consisting 209 healthy fertile women recruited from the ABC School of Medicine. The LHβ G1502A polymorphism was studied by RPLP-PCR (restriction fragment length polymorphism-polymerase chain reaction).

Results

Genotypes GG, GA and AA of the LHβ G1502A polymorphism presented frequencies of 54.6%, 31.8% and 13.6%, respectively, in the women with endometriosis (p = 0.0398); of 52.4%, 38.1% and 9.5% (p = 0.0123), respectively, in the infertile women without endometriosis; and of 68.9%, 21.5% and 9.6%, respectively, in the control group. In patients with minimal/mild endometriosis and moderate/severe endometriosis, the GG, GA and AA genotype frequencies were, respectively, 47.3%, 36.4% and 16.3% (p = 0.0118); and 61.8%, 27.3% and 10.9% (p = 0.5975). Considering the alleles, allele G was present in 70.5% of the patients with endometriosis, 71.4%% of the infertile women without endometriosis and in 79.7% of the controls, whereas allele A was present in 29.5%, 28.6% and 20.3%, respectively, in the infertile women with endometriosis (p = 0.0121), infertile women without endometriosis (p = 0.0409) and controls. Alleles G and A presented frequencies of 65.5% and 34.5% and 75.5% and 24.5%, respectively, in minimal/mild endometriosis (p = 0.0026) and moderate/severe endometriosis (p = 0.4062).

Conclusion

The data suggest that LHβ G1502A polymorphism may be involved in the predisposition to infertility and minimal/mild endometriosis-associated infertility, although endometriosis might be only a coincidental finding along with infertility.     

Clinicopathological prognostic factors and the role of cytoreduction in surgical stage IVb endometrial cancer: A retrospective multi-institutional analysis of 248 patients in Japan

Objective

To evaluate clinicopathological prognostic factors and the impact of cytoreduction in patients with surgical stage IVb endometrial cancer (EMCA).

Methods

The records of 248 patients with stage IVb EMCA who underwent primary surgery including hysterectomy at multiple institutions from 1996 to 2005 were retrospectively analyzed. Data regarding disease distribution, surgical procedures, adjuvant therapy, and survival times were collected. Univariate and multivariate analyses were performed to identify factors associated with overall survival (OS).

Results

The median OS was 24 months. The most common histological types were endometrioid (grade 1: 15%, grade 2: 20%, grade 3: 24%) and serous (17%). The most common sites of intra-abdominal metastases were pelvis (65%), ovaries (58%), omentum (58%), retroperitoneal lymph nodes (52%), and upper abdominal peritoneum (44%). In 93 patients with extra-abdominal metastases, the most common site was the lung (n = 49). Complete resection of extra-abdominal metastases was achieved in only 13 patients. Complete resection of intra-abdominal metastases was achieved in 101 patients, 52 had ≤ 1 cm residual disease, and 95 had > 1 cm residual disease; the median OS times in these groups were 48, 23, and 14 months, respectively (p < 0.0001). Multivariate analysis showed that performance status, histology/grade, adjuvant treatment, and intra-abdominal residual disease were independent prognostic factors. Intra-abdominal residual disease was an independent prognostic factor in patients with and without extra-abdominal metastases.

Conclusions

Cytoreductive surgery and adjuvant therapy may improve survival in stage IVb EMCA, particularly in patients with favorable prognostic factors, even in the presence of extra-abdominal metastases.     

The functional reconstruction of fertility-sparing radical abdominal trachelectomy for early stage cervical carcinoma

Objective

To study the feasibility and outcome of functional reconstruction during radical abdominal trachelectomy in the treatment of early stage cervical carcinoma.

Study design

Ten cervical cancer patients (FIGO stage IA2 or IB1 with tumours less than 2 cm in diameter) who desired to preserve their fertility underwent abdominal radical trachelectomy with functional reconstruction, including preserving the ascending uterine artery, placing a stent to avoid intrauterine adhesions and using three pieces of mesh to prevent cervical incompetence and uterine prolapse.

Results

The mean age of the patients was 29 years (range 28-30). The average operative time was 261 min (range 204-345), with a mean blood loss of 370 ml (range 150-500). The mean time to remove the urinary catheter was 12 days (range 8-14) after surgery and the mean time to remove pelvic drainage was 4 days (range 2-8). During the follow-up (range 4-68 months), no recurrence was detected and a normal menstrual pattern resumed within 8 weeks after surgery. No abnormality was noted in the preserved ascending branches of the uterine arteries, and no intrauterine adhesion was found. One patient successfully conceived without reproductive assistance and another patient conceived with in vitro fertilization. There was no cervical incompetence or premature rupture of membrane in their pregnancies, and cesarean sections were done as in normal women at a gestation of 38⁺⁵ weeks and 34⁺³ weeks, respectively.

Conclusion

We conclude that the functional reconstruction is a good choice of fertility-sparing surgery for patients with early stage cervical carcinoma.     

Symptomatic pelvic hematoma following transvaginal reconstructive pelvic surgery: incidence, clinical presentation, risk factors, and outcome

Objective

To assess the incidence, clinical presentation, risk factors and outcome of symptomatic pelvic hematomas following transvaginal pelvic reconstructive surgery.

Materials and methods

We reviewed the medical records of all women undergoing transvaginal reconstructive pelvic surgery in our institution between January 2006 and July 2009.

Results

462 patients underwent pelvic reconstructive surgery, of whom 28 (6%) presented with symptomatic pelvic hematomas. All cases occurred after transvaginal hysterectomy, 25 (90%) presented with fever, 20 (71%) with pelvic pain and 5 (20%) with urinary retention. All hematomas were diagnosed by ultrasound. They were located at the vaginal cuff in 18 (64%), anterior vaginal wall in six (21%) and posterior vaginal wall in four patients (14%), and had a mean volume of 590 ± 140 cm³. Laboratory data included leukocytosis (71%), thrombocytosis (57%) and elevated liver enzymes (18%). Nine patients (33%) required ultrasound-guided drainage of the hematoma, which resulted in marked clinical improvement. Surgical outcome was not affected by the presence of pelvic hematoma.

Conclusions

A postoperative symptomatic pelvic hematoma is not rare and is closely related to transvaginal hysterectomy. Its clinical presentation includes fever, pelvic pain, leukocytosis, thrombocytosis and occasionally liver dysfunction. Surgical outcome is generally unaffected.     

Luteal phase support may improve pregnancy outcomes during intrauterine insemination cycles

Objectives

To determine the impact of luteal phase support with vaginal progesterone on pregnancy outcomes in infertile couples undergoing intrauterine insemination when recombinant follicle-stimulating hormone was used for ovulation induction.

Study design

This prospective randomized study was undertaken at the Infertility Unit, Armed Forces Hospital Southern Region, Kingdom of Saudi Arabia, and included 71 patients with either primary or secondary infertility who met the inclusion criteria. All 71 patients underwent intrauterine insemination. Thirty-seven were randomized to start with a supported cycle and 34 started with an unsupported cycle. In supported cycles, patients received vaginal progesterone once daily from the day after insemination for 14 days. No progesterone was given during unsupported cycles. For the second cycle, crossover occurred such that women who initially had a supported cycle underwent an unsupported cycle, and vice versa. The cycle types were alternated until the end of the study. The main outcome measures were clinical pregnancy rates and livebirth rates per cycle and per patient.

Results

In total, 132 supported cycles and 126 unsupported cycles were performed successfully. The clinical pregnancy rate per patient was higher for supported than unsupported cycles (54.92% vs. 35.21%, respectively; p = 0.016), but the per-cycle difference was not significant (29.54% vs. 19.84%, respectively; p = 0.07). Twenty-five pregnancies in supported cycles and seven pregnancies in unsupported cycles resulted in live births. When these rates were compared per cycle and per patient, significant differences were detected between the cycle types (18.9% and 35.2% vs. 5.5% and 9.8%; p = 0.001 and <0.001, respectively).

Conclusion

Luteal phase support with vaginal progesterone improved the success of intrauterine insemination cycles when recombinant follicle-stimulating hormone was used for ovulation induction.

Condensation

Luteal phase support may improve pregnancy outcomes during intrauterine insemination cycles, but large multicentre, placebo-controlled, double-blind trials are needed.     

The efficacy and tolerability of short-term low-dose estrogen-only add-back therapy during post-operative GnRH agonist treatment for endometriosis

Objective

To evaluate the efficacy and tolerability of a low-dose estrogen-only regimen as a short-term add-back therapy during post-operative GnRH agonist (GnRHa) treatment of patients with endometriosis.

Study design

Retrospective cohort study. One hundred seventeen women of reproductive age who were treated with post-operative GnRHa after conservative laparoscopic surgery for endometrioma were eligible for this study. The patients were divided into two groups: group A (n = 56) received tibolone (2.5 mg) between 2002 and 2004 and group B (n = 61) received estradiol valerate (1 mg) between 2005 and 2007 as an add-back therapy for five months, beginning at the time of the second injection of a GnRHa. The incidence of hypoestrogenic symptoms and the degree of pelvic pain according to a verbal rating scale (VRS) scoring system, the incidence and patterns of uterine bleeding during add-back therapy, the endometrial thickness by ultrasonography two months after the last GnRHa treatment, and the serum CA-125 level were evaluated.

Results

The incidence of uterine bleeding, hypoestrogenic symptoms such as hot flashes and sweating, and pelvic pain did not differ significantly between the two treatment groups. However, the endometrium was thicker in group A than group B (p = 0.022). In group B, the frequency of uterine bleeding was lower from the second month after starting add-back therapy than in group A, but without statistical significance (at the sixth month, p = 0.086).

Conclusion

The low-dose estrogen-only regimen was efficacious and tolerable as a short-term add-back therapy during post-operative GnRHa treatment after surgery for endometriosis.