A randomized controlled trial of tubal flushing with lipiodol for unexplained infertility.

OBJECTIVE: To test the hypothesis that, in couples with unexplained infertility, tubal flushing with an oil-soluble media (lipiodol) would increase the pregnancy rate within 6 months compared with expectant management. DESIGN: A prospective, randomized, controlled study in which couples were allocated to either a single treatment with lipiodol or no further action. SETTING: Two tertiary referral centers for assisted reproduction. PATIENT(S): Couples with a diagnosis of primary or secondary unexplained infertility based on a normal semen analysis according to World Health Organization criteria, patent fallopian tubes at hysterosalpingography or laparoscopy, and ovulatory menstrual cycles based on midluteal phase progesterone levels or ultrasonic follicle tracking. INTERVENTION(S): In those patients randomized to lipiodol, a single treatment was performed. MAIN OUTCOME MEASURE(S): Biochemical (i.e., positive pregnancy test) and clinical (i.e., fetal heart on ultrasound scan) pregnancy rates. RESULT(S): Seventeen couples were randomized to lipiodol and 17 to expectant treatment. The higher pregnancy rate after lipiodol was statistically significant. There were no complications after lipiodol treatment. CONCLUSION(S): There was a statistically significantly higher pregnancy rate in couples with unexplained infertility randomized to a single tubal flush with lipiodol compared with no treatment.     

Characterizing the endometrium in unexplained and tubal factor infertility: a multiparametric investigation

OBJECTIVE: To characterize endometrial development in unexplained and tubal factor infertility. DESIGN: Prospective study of 20 women with unexplained infertility, 22 with tubal factor infertility, and 21 fertile controls in the midproliferative, periovulatory, and midluteal phases of the menstrual cycle. SETTING: Reproductive Medicine Department of St. Mary's Hospital, Manchester, United Kingdom. PATIENT(S): Women awaiting assisted conception. INVESTIGATION(S): Serum hormone assays, transvaginal ultrasound, Doppler, and midluteal endometrial biopsies. MAIN OUTCOME MEASURE(S): Serum levels of E2, P, and LH, endometrial ultrasound morphometry, uterine and subendometrial artery Doppler, and endometrial histology and biochemistry. RESULT(S): Women with unexplained infertility demonstrated significantly reduced uterine artery flow velocity in all phases, significantly elevated uterine and subendometrial artery impedance in the periovulatory and midluteal phases, and significantly reduced endometrial texture in the midproliferative phase. Women with tubal factor infertility demonstrated significantly reduced uterine artery flow velocity, without a concomitant increase in impedance, and significantly greater expression of endometrial glandular and luminal keratan sulphate. CONCLUSION(S): Unexplained infertility is associated with a profound impairment of endometrial perfusion that might be amenable to treatment by perfusion enhancers. Tubal factor infertility is associated with endometrial developmental defects that might be corrected by salpingectomy. Endometrial ultrasound and Doppler studies are likely to become a vital tool in the investigation of infertility.     

Laparoscopy for the treatment of unexplained infertility

Aim:  To determine the best treatment for unexplained infertility.
Methods:  A retrospective study was used to examine Japanese women with unexplained infertility that had undergone laparoscopy. The main outcome measure of the study was the rate of pregnancy after laparoscopy.
Results:  One hundred and thirty-eight women diagnosed with unexplained infertility received laparoscopy and as a result 55 women had their diagnosis of unexplained infertility confirmed. There were no statistically significant differences between the women who became pregnant after laparoscopy in terms of duration of infertility, duration of treatment or age. The pregnancy rate of women with unexplained infertility was 56.4%, with 90% of these pregnancies achieved within the first 6 months. There were 64 women with minor endometriosis considered to be suffering from unexplained infertility before laparoscopy. The characteristics of the patients in the unexplained infertility group and in the minor endometriosis group were similar, but patients with minor endometriosis were found to have a lower pregnancy rate compared to those with unexplained infertility (35.9% vs 56.4%; P  = 0.02).
Conclusions:  The effective period after laparoscopy appears to be 6 months. Assisted reproductive technology should be considered after that time. Pregnancy rates were low in women with minor endometriosis compared with unexplained infertility. It is important to clarify the cause of infertility using laparoscopy. (Reprod Med Biol 2006; 5 : 59–64)     

Fallopian tube sperm perfusion versus intrauterine insemination in unexplained infertility: a randomized, prospective, cross-over trial

OBJECTIVE: To compare the results of fallopian tube sperm perfusion (FSP) versus standard intrauterine insemination (IUI) in patients with unexplained infertility undergoing controlled ovarian hyperstimulation (COH). DESIGN: Randomized, prospective, cross-over study. SETTING: Reproductive medicine unit of a university hospital. PATIENT(S): Fifty-six couples with unexplained infertility. INTERVENTION(S): COH was induced by recombinant FSH and monitored by serial transvaginal ultrasound. On the day of hCG administration during the first treatment cycle, patients were randomized to either IUI or FSP. Thereafter, in case no pregnancy was achieved, patients went on being treated with FSP and IUI in alternate cycles. A maximum of four treatment cycles per couple was performed. FSP was performed using a pediatric Foley's catheter inseminating 4 mL of sperm-enriched suspension; a Kremer-Delafontaine catheter delivering 0.5 mL of sperm suspension was used for IUI. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate per cycle. RESULT(S): One hundred twenty-seven cycles (58 FSP, 69 IUI) were performed. The clinical pregnancy rate per cycle was 21.7% for IUI and 8.6% for FSP, respectively. No major adverse effects were recorded for either technique. CONCLUSION(S): After COH, FSP is less effective than IUI in couples with unexplained infertility.     

Prediction of laparoscopic surgery outcomes in tubal infertility

This study aimed to elucidate the predictive value of hysterosalpingography (HSG) and laparoscopy (LS) scores for spontaneous pregnancy after laparoscopic surgery in 50 patients with tubal infertility. During a 1-year follow-up period, 28% of these patients became pregnant. Both scores were informative in prediction of pregnancy with the area under the ROC curve being 0.80 (95% CI 0.67-0.93) and 0.74 (95% CI 0.58-0.89) for LS and HSG scores, respectively.     

A simple method for fallopian tube sperm perfusion using a blocking device in the treatment of unexplained infertility

Objective: To evaluate the efficacy of fallopian sperm perfusion (FSP) using a new method similar to the FAST system® in comparison with standard intrauterine insemination (IUI) in patients with unexplained infertility.

Design: Prospective, randomized, controlled study.

Setting: Assisted conception service in a University Hospital.

Patient(s): Women with unexplained infertility undergoing controlled ovarian hyperstimulation (COH).

Intervention(s): After hCG administration, patients were randomized to either standard IUI or FSP. The women received the same treatment in the first and all subsequent cycles. A maximum of three cycles was performed. Intrauterine insemination was performed using a standard method, and fallopian sperm perfusion was performed using a commercial device for hysterosalpingography and tubal hydropertubation.

Main Outcome Measure(s): Clinical and ongoing pregnancy rates.

Result(s): A total of 132 cycles was completed: 66 IUI cycles and 66 FSP cycles. In the IUI group, there were 5 ongoing pregnancies, giving a pregnancy rate of 7.6 per cycle and 15.6% per patient; in the FSP group, 14 ongoing pregnancies occurred, giving a pregnancy rate of 21.2% per cycle and 42.4% per patient. The prevalence of multiple pregnancies, miscarriages and ectopic pregnancies was similar in the two insemination groups. Fallopian sperm perfusion was easy to perform, and no case of sperm reflux was observed. The procedure was well tolerated and no complications were observed. The costs were comparable with standard IUI.

Conclusion(s): In the treatment of couples with unexplained infertility, the method for fallopian sperm perfusion described yields higher pregnancy rates than IUI, with no significant increase in costs or complications. However, these results need to be confirmed in larger studies before replacing IUI with FSP as standard practice.     

An update on surgical management of tubal disease and infertility

Reproductive surgery remains an important option and is complementary to assisted reproductive technologies. A spectrum of tubal disease of varying severity is recognized at laparoscopy. Pathology may vary from peritubal adhesions, damaged fimbriae or distorted tubal anatomy to tubal blockage or hydrosalpinx (a fluid-filled distension of the fallopian tube in the presence of distal tubal occlusion).Reproductive surgery should be considered as first-line treatment: when the correction of infertility pathology is achievable and a good result is expected; when the pathology is causing the patient pain or discomfort; and when if left uncorrected infertility pathology will compromise the results or increase the risks of assisted reproductive technology. The success of surgical infertility treatment depends on the careful selection of cases using appropriate investigative techniques, with procedures performed in centres with sufficient expertise. For both specialized reproductive and general gynaecological surgery, it is paramount to follow strict microsurgical principles to avoid adhesion formation and conserve normal tubal and ovarian tissues.     

Importance of endometrial quality in women with tubal infertility during a natural menstrual cycle for the outcome of IVF treatment

Purpose: The importance of endometrial maturation at estimated time of implantation for the outcome of IVF treatment in regularly menstruating women with tubal infertility was evaluated. Methods: FSH was measured on cycle day 3, on days 10–15 urine and blood were collected to estimate the day of the LH peak, and E₂ and P₄ were measured during the luteal phase, on cycle days 19–26. An endometrial biopsy was obtained on days LH + 3 to LH + 6. Results: The number of subjects with delayed endometrial maturation was larger in the group of infertile women who did not become pregnant compared to pregnant women and controls. Those infertile women who did not become pregnant after IVF treatment also presented with a higher basal FSH on cycle day 3 and lower E₂ and P₄ AUC in the luteal phase. Six infertile women and two controls presented with mid- and late-proliferative endometrium in the luteal phase on cycle days LH + 3 to LH + 6, in the presence of adequate E₂ and P₄ secretion. Six morphological characteristics were compared in the three groups: (1) 17 infertile women who became pregnant, (2) 18 who did not become pregnant, and (3) 28 controls. The pregnant infertile women did not differ from the controls. The numbers of glandular and stromal mitoses were significantly higher in those women who did not become pregnant (P<0.01) compared with those who became pregnant. Endometrial biopsies obtained on cycle days LH + 5 and LH + 6 showed significant differences in glandular epithelial height (P<0.05) and number of vacuolated cells among the nonpregnant women (P<0.01), the pregnant women (P<0.05), and controls. Conclusions: A higher frequency of retarded endometrial development in women who did not become pregnant following IVF treatment was found. In some cases, endometrial insensitivity could most likely cause retarded endometrial development and failure of implantation after IVF treatment, which could not be overcome by routine luteal-phase support. However, our results do not allow conclusions concerning its relative importance compared to preembryo quality; this has to be investigated further.     

Association of Chlamydia trachomatis serology with tubal infertility in Nigerian women

AIM: To determine the association between tubal infertility and Chlamydia trachomatis in Nigerian women. METHODS: This case-control study is from the Departments of Obstetrics and Gynecology of two tertiary hospitals in Nigeria. One hundred and sixty-two infertile patients with tubal occlusion had 162 pregnant women matched for age as controls. Information on sociodemographic variables, sexual and reproductive risk factors, and history of previous pelvic infections were elicited using a study protocol. The prevalence of Chlamydia Trachomatis antibody was determined for cases and controls. RESULTS: The prevalence of serum Chlamydia antibody was significantly higher in cases (65.8%) compared with controls (17.3%; P < 001). The effects of Chlamydia antibodies on infertility were strengthened in the multivariate model controlling for Chlamydia antibodies and gynecologic symptoms, compared to the univariate model. However, the association was attenuated and non-significant when the effects of gynecologic symptoms, sociodemographic characteristics, contraceptive and sexual history were controlled in the conditional logistic regression model. The strongest independent predictors of infertility in the model were vaginal discharge, education less than tertiary and more than three lifetime sexual partners (proxies of sexually transmitted infections). CONCLUSIONS: There was no strong independent association between Chlamydia antibodies and the risk of being infertile in Nigerian women. By contrast, the proxies of sexually transmitted infections were significant predictors of infertility in the women. Efforts to address these factors, which are proxies of sexually transmissible infections, Chlamydia infection, and health-seeking behavior for these infections, will likely contribute to reducing the burden of infertility in Nigerian women.     

Effect of tubal ligation on ovarian reserve and the ovarian stromal blood supply

AIM: Our aim was to evaluate possible adverse effects of tubal ligation on ovarian reserve and ovarian stromal vascular support. METHODS: Ninety-one women who underwent tubal ligation, using a modified Pomeroy technique, were studied. The main outcome measurements were serum follicle stimulating hormone, luteinising hormone and oestradiol levels, ovarian volume, number of antral follicles and Doppler study of ovarian stromal artery on the third day of the menstrual cycle immediately before, 1 month and 12 months after the surgical intervention. RESULTS: Statistically significant elevation of follicle stimulating hormone levels was observed at 1 and 12 months after tubal ligation (P < 0.05). CONCLUSION: Doppler flow studies of the ovarian stromal arteries showed that there were no significant differences before and after tubal ligation.     

After the FLUSH trial: a prospective observational study of lipiodol flushing as an innovative treatment for unexplained and endometriosis-related infertility

OBJECTIVES: To assess the demographics, efficacy and safety of lipiodol flushing fertility treatment. DESIGN: Prospective observational study. SETTING: Secondary level care infertility clinic and radiology centre based in Auckland, New Zealand. POPULATION: The first cohort of 100 New Zealand women with infertility to undergo lipiodol flushing as an innovative fertility treatment. METHODS: Women received lipiodol flushing performed by a hysterosalpingogram technique and were followed up at 6 months. MAIN OUTCOME MEASURES: Clinical pregnancy at 6 months post-treatment; and live birth or ongoing pregnancy. RESULTS: The overall pregnancy rate was 30% and the live birth or ongoing pregnancy rate 27%. For women under 40 years old, a 32% pregnancy rate and a 25% live birth or ongoing pregnancy rate were seen in women with unexplained infertility, and a 50% pregnancy rate and a 47% live birth or ongoing pregnancy rate were seen in women with endometriosis. Of women aged 40 years and older, the pregnancy rate was 13% and the live birth or ongoing pregnancy rate was 13%. The pregnancy rates included those occurring after additional interventions, such as intrauterine insemination and in vitro fertilisation, accounting for 12 of the 30 pregnancies. There were no treatment complications. CONCLUSION: This study provides further evidence of the efficacy and safety of lipiodol flushing fertility treatment.     

159对接受助孕治疗不孕症夫妇支原体和衣原体感染情况分析

目的探讨接受助孕治疗的不孕症夫妇支原体和衣原体携带情况及其与体外受精／卵细胞质内单精子注射结局的关系。方法选择2009年3月至2011年9月北京大学第一医院生殖与遗传医疗中心无下生殖道感染症状且接受助孕治疗的159对不孕症夫妇,在取卵日或人工授精日分别取宫颈分泌物和精液,采用聚合酶链反应（PCR）法进行支原体和衣原体的检测。结果女性患者支原体阳性29例（18．200,29／159）,其中解脲支原体（ureaplasma urealyticum,UU）和人型支原体（mycoplasma hominis,Mh）分别为26例（16．4％,26／159）和3例（1．9％,3／159）,未检出衣原体。男性患者支原体阳性4例（2．5％,4／159）,均为UU;衣原体阳性3例（1．9％,3／159）。输卵管性不孕症患者支原体阳性10例（16．9％,10／59）,非输卵管性不孕症患者支原体阳性19例（19．0％,19／100）,两者比较,差异无统计学意义（P〉0．05）。女性支原体阴性组和阳性组的获卵数[（11．8±6．0）个,（14．6±6．2）个]、优质胚胎率（37．6％,43．2％）和临床妊娠率（48．2％,30．0％）比较,差异无统计学意义（P〉0．05）。结论进入助孕治疗周期的不孕症夫妇仍有一定的生殖道支原体和衣原体携带率,支原体携带与临床妊娠结局无明显关系。     

不明原因不孕患者体外受精方式的探讨

目的探讨不明原因不孕患者行首次体外受精(IVF)治疗时受精方式的选择。方法对2004年6月至2005年12月在北京大学第三医院行IVF治疗的35例不明原因不孕患者,将其卵母细胞分为2组,同时行常规受精和卵胞浆内单精子注射受精(ICSI),比较2组的受精结局、妊娠率及着床率。结果常规受精组受精率(51.2%)低于ICSI组(61.3%),差异有统计学意义(P<0.05);而完全受精失败率(20.0%)明显高于ICSI组(2.8%),差异有统计学意义(P<0.05);2组的优质胚胎率、临床妊娠率、着床率差异无统计学意义。结论不明原因不孕患者行首次IVF治疗时,采用部分卵母细胞常规受精、部分卵母细胞ICSI的方法,可降低完全受精失败风险。