Cabergoline versus calcium infusion in the prevention of ovarian hyperstimulation syndrome: a randomised controlled study.

The aim of this study was to compare the efficacy of calcium infusion versus cabergoline in the prevention of ovarian hyperstimulation syndrome (OHSS) in IVF patients at high risk for OHSS. One hundred and seventy patients who were stimulated using the long luteal GnRH agonist protocol and at high risk for developing OHSS were randomised in a 1:1 ratio to cabergoline group and calcium gluconate group. In cabergoline group, 0.5 mg of cabergoline was administered once daily p.o. for eight days starting on the day of HCG administration. In calcium gluconate group, intravenous calcium gluconate (10%, 10 ml in 200 ml of physiologic saline) was administered daily for four days starting on the day of ovum pickup. Six patients in cabergoline group and eight patients in calcium gluconate group developed moderate OHSS. One patient in each group developed severe OHSS. The incidence of moderate/severe OHSS was comparable between both groups (8.24% vs. 10.59%, p value = .599, OR = 0.76, 95% CI [0.269-2.138]). The implantation, clinical and ongoing pregnancy rates were similar in the two groups (16.91% vs. 15.84%, p = .771, 35.29% vs. 32.94%, p = .746, and 30.59% vs. 28.24%, p = .736, respectively). In conclusion, calcium infusion and cabergoline have comparable effectiveness in the prevention of OHSS. Both drugs are well tolerated, cheap and have no adverse effects on the reproductive outcomes of IVF cycle.Clinical trial registration: The trial was registered on clinical trials.gov database [NCT02875587].Impact StatementWhat is already known on this subject? The effectiveness of cabergoline in the prevention of OHSS in IVF patients at high risk for OHSS is confirmed by overwhelming scientific evidence. Calcium infusion is a novel strategy for prevention of OHSS. Few studies reported the use of calcium infusion in the prevention of OHSS. A retrospective study and a randomised controlled study revealed that calcium infusion reduces the incidence of OHSS. Moreover, a quasi-randomised study revealed that calcium infusion is as effective as cabergoline in the prevention of OHSS.What the results of this study add? Calcium infusion and cabergoline have comparable effectiveness in the prevention of OHSS. Both drugs are well tolerated, cheap and have no adverse effects on the reproductive outcomes of IVF cycle.What the implications are of these findings for clinical practice and/or further research? Calcium infusion should be used to minimise the incidence of OHSS in IVF patients at high risk for OHSS.

Extended doxycycline treatment versus salpingectomy in the management of patients with hydrosalpinx undergoing IVF-ET.

BACKGROUND: The aim of this study was to determine whether the treatment with doxycycline before and after oocyte retrieval is as effective as salpingectomy in minimizing the detrimental effect of hydrosalpinx on the outcomes of IVF-ET. METHODS: A retrospective analysis was done for the outcomes of the IVF-ET cycles of patients with hydrosalpinx who underwent laparoscopic salpingectomy prior to IVF cycle (n = 260) or were treated with extended doxycycline treatment during the IVF cycle (n = 45). In doxycycline group, doxycycline (100 mg twice daily) was started 1 week before anticipated oocyte retrieval and was continued for 1 week after oocyte retrieval. In salpingectomy group, the mesosalpinx was coagulated as close as possible to the fallopian tube. RESULTS: The implantation, clinical pregnancy, ongoing pregnancy and live birth rates were significantly higher in the salpingectomy group (20.87% Vs. 9.91%, P value =0.007, 44.62% Vs. 20%, P value = 0.002, 39.62% Vs. 17.78%, P value = 0.005 and 37.31% Vs. 15.56%, P value = 0.005 respectively). CONCLUSION: Salpingectomy is more effective than extended doxycycline treatment in improving the outcomes of IVF-ET in patients with hydrosalpinx undergoing IVF-ET. Further, larger well designed randomized controlled trials should be conducted to confirm the findings of this study.

Misoprostol Prior to Diagnostic Office Hysteroscopy in the Subgroup of Patients with No Risk Factors for Cervical Stenosis: A Randomized Double Blind Placebo-Controlled Trial.

AIMS: To assess the effectiveness of vaginal misoprostol in minimizing the pain perceived by patients with no risk factors for cervical stenosis (i.e., parous women of reproductive age who have no history of cesarean section or cervical surgery) during diagnostic office hysteroscopy. METHODS: A total of 100 patients with no risk factors for cervical stenosis were randomized to the misoprostol group (n = 50) or the placebo group (n = 50). In the misoprostol group, 2 misoprostol tablets (400 µg) were administered vaginally 12 h before office hysteroscopy. In the placebo group, 2 placebo tablets were administered. The patients rated the intensity of pain perceived during the procedure and at 30 min after the procedure with the use of a 100 mm visual analog scale (VAS). The hysteroscopists also scored the difficulty of hysteroscope insertion into the uterine cavity with the use of a 100 mm VAS. RESULTS: There were no significant differences between both groups in the VAS pain scores during or at 30 min after the procedure (28.3 ± 13.58 vs. 30.42 ± 15.13 and 11.1 ± 10.23 vs. 13.32 ± 11.12, respectively). The difficulty of hysteroscope insertion into the uterine cavity was comparable between both groups. CONCLUSION: Misoprostol administration prior to diagnostic office hysteroscopy appears to have no beneficial role in the subgroup of patients with no risk factors for cervical stenosis.

Misoprostol versus uterine straightening by bladder distension for pain relief in postmenopausal patients undergoing diagnostic office hysteroscopy: a randomised controlled non-inferiority trial.

OBJECTIVE: To compare the effectiveness of misoprostol with uterine straightening by bladder distension in minimising the pain experienced by postmenopausal patients during diagnostic office hysteroscopy. STUDY DESIGN: Seventy-six postmenopausal patients were randomly allocated in a 1:1 ratio to the misoprostol group or to the bladder distension group. Patients in the misoprostol group were instructed to insert two misoprostol tablets (400µg) in the vagina 12h before office hysteroscopy. Patients in the bladder distension group were instructed to drink one litre of water and to avoid urination during a period of 2h before office hysteroscopy. The severity of pain experienced by the patients during and at 30min after the procedure was measured using a 100-mm visual analogue scale (VAS). The ease of passing the hysteroscope through the cervical canal was assessed by the hysteroscopists using a 100-mm VAS. RESULTS: The passage of the hysteroscope through the cervical canal was easier in the misoprostol group [60.37±15.78 vs. 50.05±19.88, p=0.015]. The mean VAS pain score during the procedure was significantly lower in the misoprostol group [39.47±13.96 vs. 50.18±15.44, p=0.002]. The mean VAS pain score 30min post-procedure was comparable between both groups [11.82±3.71 vs. 12.61±4.06, p=0.379]. CONCLUSION: Vaginal misoprostol is more effective than uterine straightening by bladder distension in relieving the pain experienced by postmenopausal patients during office hysteroscopy. TRIAL REGISTRATION: Clinicaltrials.gov [NCT02328495]. https://clinicaltrials.gov/ct2/show/NCT02328495.

Barbed Versus Conventional Suture: A Randomized Trial for Suturing the Endometrioma Bed After Laparoscopic Excision of Ovarian Endometrioma.

OBJECTIVES: To determine whether the unidirectional knotless barbed suture can be used to control bleeding from the endometrioma bed after laparoscopic excision of ovarian endometrioma, and to detect whether the use of the unidirectional barbed suture is associated with shorter suturing time of the endometrioma bed compared with the continuous conventional smooth suture with intracorporeal knot tying. DESIGN: Randomized clinical trial (Canadian Task Force classification I). SETTING: Tertiary hospital. PATIENTS: Forty patients with unilateral ovarian endometrioma (mean diameter, 3-10 cm) were randomized in a 1:1 ratio to the barbed suture group or the conventional suture group. INTERVENTIONS: The endometrioma bed was sutured either with unidirectional barbed suture (V-Loc 180; Covidien, Mansfield, MA) or conventional suture (Vicryl; Ethicon, Somerville, NJ). Two layers of continuous sutures were used to control bleeding from the endometrioma bed and to reapproximate the ovarian edges. MEASUREMENTS AND MAIN RESULTS: The degree of suturing difficulty was evaluated by the surgeons using a visual analog scale (VAS) ranging from 1 (least difficult suturing) to 10 (most difficult suturing). Operating time and suturing time were significantly shorter in the barbed suture group (43.3 ± 10.54 vs 52.8 ± 9.69 minutes; p = .005 and 8.85 ± 2.52 vs 15.7 ± 4.12 minutes; p < .001, respectively). Suturing with barbed suture was less difficult than suturing with conventional suture (3.68 ± 1.37 vs 4.77 ± 1.56; p = .025). Intraoperative blood loss was similar in the 2 groups. No perioperative complications were reported in either group. A nonsignificant decrease in serum anti-mullerian hormone (AMH) levels was observed after the operation in the barbed suture group and the conventional suture group (3.04 ± 1.5 vs 2.52 ± 1.31 ng/mL; p = .252 and 2.76 ± 1.48 vs 2.13 ± 1.14 ng/mL; p = .139, respectively). The rate of decline in serum AMH levels after the operation was 18.32% in the barbed suture group and 22.84% in the conventional suture group. CONCLUSION: The unidirectional knotless barbed suture (V-Loc) facilitates suturing of the endometrioma bed after laparoscopic excision of ovarian endometrioma. Compared with conventional smooth suture (Vicryl), the unidirectional barbed suture reduces the time needed to suture the endometrioma bed and the total operating time.

GnRH antagonist rescue protocol combined with cabergoline versus cabergoline alone in the prevention of ovarian hyperstimulation syndrome: a randomized controlled trial.

BACKGROUND: The aim of this study was to compare the efficacy of antagonist rescue protocol (replacing GnRH agonist with GnRH antagonist and reducing the dose of gonadotropins) combined with cabergoline versus cabergoline alone in the prevention of ovarian hyperstimulation syndrome (OHSS) in patients pretreated with GnRH agonist long protocol who were at high risk for OHSS. METHODS: Two hundred and thirty six patients were randomized in a 1:1 ratio to the cabergoline group or the antagonist rescue combined with cabergoline group. Both groups received oral cabergoline (0.5 mg/day) for eight days beginning on the day of HCG administration. In the antagonist rescue combined with cabergoline group, when the leading follicle reached 16 mm, GnRH agonist (triptorelin) was replaced with GnRH antagonist (cetrorelix acetate) and the dose of HP-uFSH was reduced to 75 IU/day. HCG (5,000 IU/I.M) was administered when the serum estradiol level dropped below 3500 pg/ml. The study was open label and the outcome assessors (laboratory staff and the doctor who performed oocyte retrieval) were blind to treatment allocation. RESULTS: The incidence of moderate/severe OHSS was significantly lower in the antagonist rescue combined with cabergoline group [5.08 % Vs 13.56 %, P value =0.025, OR = 0.342, 95 % CI, 0.129-0.906]. Four cycles were cancelled in the cabergoline group. There were no significant differences between the groups with respect to the number of retrieved oocytes, metaphase II oocytes, high quality embryos and fertilization rate. Moreover, the implantation and pregnancy rates were comparable between both groups. CONCLUSION: GnRH antagonist rescue protocol combined with cabergoline is more effective than cabergoline alone in the prevention of OHSS. TRIAL REGISTRATION: Clinical trial.gov ( NCT02461875 ).

Optimal timing of misoprostol administration in nulliparous women undergoing office hysteroscopy: a randomized double-blind placebo-controlled study.

OBJECTIVE: To determine the optimal timing of vaginal misoprostol administration in nulliparous women undergoing office hysteroscopy. DESIGN: Randomized double-blind placebo-controlled study. SETTING: University teaching hospital. PATIENT(S): One hundred twenty nulliparous patients were randomly allocated in a 1:1 ratio to the long-interval misoprostol group or the short-interval misoprostol group. INTERVENTION(S): In the long-interval misoprostol group, two misoprostol tablets (400 µg) and two placebo tablets were administered vaginally at 12 and 3 hours, respectively, before office hysteroscopy. In the short-interval misoprostol group, two placebo tablets and two misoprostol tablets (400 µg) were administered vaginally 12 and 3 hours, respectively, before office hysteroscopy. MAIN OUTCOME MEASURE(S): The severity of pain was assessed by the patients with the use of a 100-mm visual analog scale (VAS). The operators assessed the ease of the passage of the hysteroscope through the cervical canal with the use of a 100-mm VAS as well. RESULT(S): Pain scores during the procedure were significantly lower in the long-interval misoprostol group (37.98 ± 13.13 vs. 51.98 ± 20.68). In contrast, the pain scores 30 minutes after the procedure were similar between the two groups (11.92 ± 7.22 vs. 13.3 ± 6.73). Moreover, the passage of the hysteroscope through the cervical canal was easier in the long-interval misoprostol group (48.9 ± 17.79 vs. 58.28 ± 21.85). CONCLUSION(S): Vaginal misoprostol administration 12 hours before office hysteroscopy was more effective than vaginal misoprostol administration 3 hours before office hysteroscopy in relieving pain experienced by nulliparous patients undergoing office hysteroscopy. CLINICAL TRIAL REGISTRATION NUMBER: NCT02316301.