Luteinized Unruptured Follicle Syndrome Research Articles

Optimizing timing for intrauterine insemination (IUI) in donor sperm cycles: pre- versus post-ovulation insemination in natural cycles

Purpose To investigate whether pregnancy outcomes of natural cycle intrauterine insemination (IUI) with donor sperm can be improved by performing insemination after confirmation of ovulation. Methods This retrospective cohort study evaluated 751 couples undergoing 1170 cycles of artificial insemination with donor sperm (AID) in natural cycles between January 2018 and January 2021. Patients underwent AID either within 6–12 h after spontaneous luteinizing hormone (LH) surge (pre-ovulation group) or after ovulation was confirmed by ultrasound (post-ovulation group). Propensity score matching was performed to account for differences in baseline characteristics between groups. The main outcome measures of this study were clinical pregnancy rate and live birth rate. Results After propensity score matching, each group comprised 216 cycles. No significant differences were observed between the pre-ovulation and post-ovulation groups in terms of clinical pregnancy rate (30.6% vs 27.3%, respectively, p = .458) and live birth rate (25.0% vs 22.7%, respectively, p = .651). However, upon excluding cases of luteinized unruptured follicle syndrome (LUFS) from the pre-ovulation group, the clinical pregnancy rate (33.5% vs 27.3%, respectively, p = .043) and live birth rate (27.4% vs 22.7%, respectively, p = .039) were significantly higher in the pre-ovulation group. Conclusions For fertile women undergoing AID in natural cycles, pre-ovulation insemination timing yielded superior pregnancy outcomes compared to post-ovulation insemination when ovulation was achieved. However, due to the occurrence of LUFS, pre- and post-ovulation AID resulted in comparable overall pregnancy outcomes in natural cycles.

Trends in acupuncture for infertility: a scoping review with bibliometric and visual analysis.

Unexplained recurrent implantation failure and the high cost of assisted reproductive techniques for those experiencing infertility have increasingly resulted in the use of acupuncture. However, the trends and research status of acupuncture on infertility resulting in natural conception have not been systematically summarized. This scoping review and knowledge graph analysis aimed to summarize existing clinical studies on acupuncture for infertility that resulted in natural conception. Seven databases, namely, PubMed, Embase, the Cochrane Library, CNKI, VIP, Wanfang Data, and SinoMed, were searched up to August 2023 (updated on 1 April). Two authors independently identified related clinical studies and systematic reviews, and extracted data from included studies on acupuncture for infertility; any discrepancies were resolved by discussion or judged by a third author. A meta-analysis was conducted based on randomized controlled trials (RCTs), and data were synthesized using risk ratios with 95% confidence intervals. Of the 310 articles meeting the inclusion criteria, 274 were primary studies, 7 were systematic reviews, and 29 were case reports. Reported adverse events included mild ovarian irritation and early signs of miscarriage. Out of the 274 primary studies, there were 40 (14.60%) cases of male infertility and 234 (85.40%) cases of female infertility. Current research highlights on acupuncture for infertility focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and luteinized unruptured follicle syndrome (LUFS), while acupuncture for male infertility was a hotspot in the early research stage. The meta-analysis also suggested that acupuncture was more effective than human chorionic gonadotropin (HCG) [RR = 1.89, 95% CI (1.47, 2.42), 11 RCTs, 662 participants]. Acupuncture combined with HCG was comparable to HCG [RR = 2.33, 95% CI (1.53, 3.55), four RCTs, 259 participants]. Compared with no treatment, acupuncture resulted in a higher pregnancy rate [RR = 22.12, 95% CI (1.39, 353.09), one RCT, 47 participants]. There was no statistical difference between acupuncture combined with HCG plus letrozole and HCG plus letrozole [RR = 1.56, 95% CI (0.84, 2.89), one RCT, 84 participants]. Current research highlights on acupuncture for infertility resulting in natural conception focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and LUFS, while studies on male infertility and female infertility caused by blockage in the fallopian tube, thin endometrium, and other factors were insufficient. Well-designed confirmatory clinical studies are still needed as the research hypotheses of most studies were unclear.

Meta analysis of ovulation induction effect and pregnancy outcome of acupuncture & moxibustion combined with clomiphene in patients with polycystic ovary syndrome.

Using Mesh Meta Analysis to evaluate the efficacy of Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene for treating Polycystic Ovary Syndrome (PCOS), in order to provide evidence-based medical evidence for whether to recommend Acupuncture & Moxibustion or Combine western medicine to treat PCOS. Eight databases including The Cochrane Library, Pubmed, Embase, Web of Science, CNKI, Wanfang Date, VIP and CBM were searched by computer. The included research period is from the establishment of the database to May 2023, which concerned with randomized controlled trials involving Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene on ovulation induction and pregnancy outcome in patients with PCOS. The duration of the research paper is from 2016 to 2023.The inclusion criteria refer to the Rotterdam standards issued by the European Center for Human Reproduction and Embryology and the American Society of Reproductive Medicine in January 2003, or the Expert Consensus on the Diagnosis and Treatment of Polycystic Ovarian Syndrome by the Endocrinology Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association. Simultaneously exclude related diseases, repetitive literature, as well as literature with incomplete abstract information and no original data provided. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias included in the study, using Stata17.0 software for a mesh meta-analysis. Six randomized controlled trials were included, covering 1410 PCOS patients. Three interventions included Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene. Mesh Meta Analysis showed that in terms of improving ovulation rate, there was no statistical difference between Acupuncture & Moxibustion (A), Clomiphene (B), Clomiphene combined with Acupuncture & Moxibustion (C) (P>0.05).Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=0.15,95% CI (-0.51,0.80)], Acupuncture & Moxibustion (A) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.60,95% CI (0.97,2.23)], Clomiphene (B) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.45,95% CI (0.91,1.99)]. In terms of pregnancy outcome, the difference between the three intervention methods was statistically significant (P<0.05). Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=-0.80,95% CI (-1.84,0.23)], Acupuncture & Moxibustion (A) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=0.29,95% CI (-0.73,1.30)], and Clomiphene (B) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.09,95% CI (0.39,1.79)], The order of pregnancy rate from high to low is Acupuncture & Moxibustion combined with Clomiphene (C), Acupuncture & Moxibustion (A), Clomiphene (C).In terms of influencing endometrial thickness, the difference between the three intervention methods was statistically significant (P<0.05). Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=-0.84,95% CI (-1.87,0.19)], Acupuncture & Moxibustion (A) versus Acupuncture & Moxibustion combined with Clomiphene (C) [MD=0.26,95% CI (-1.01,1.53)], Clomiphene (B) versus Acupuncture & Moxibustion combined with Clomiphene (C) [MD=1.10,95% CI (0.36,1.84)], Acupuncture & Moxibustion combined with Clomiphene (C) has the best effect on improving endometrial thickness. In subgroup analysis, the effect of Acupuncture & Moxibustion treatment frequency on ovulation rate and pregnancy rate was not statistically significant. The combination of Acupuncture & Moxibustion, Electroacupuncture and warm Acupuncture & Moxibustion has no effect on the pregnancy rate, but the combination of Electroacupuncture and Clomiphene has the best effect on improving the ovulation rate. In the observation of adverse reactions, compared with clomiphene alone, Acupuncture & Moxibustion combined with Clomiphene can reduce the occurrence of Luteinized Unruptured Follicle Syndrome (LUFS) and Ovarian Hyperstimulation Syndrome (OHSS), and reduce the occurrence of physical adverse reactions such as nausea, vomiting, headache and dermatitis. Acupuncture & Moxibustion is effective in improving the ovulation promoting effect and pregnancy outcome of PCOS patients. The ovulation promoting effect of Acupuncture & Moxibustion or combined with Clomiphene is similar to that of Clomiphene alone, but Acupuncture & Moxibustion combined with Clomiphene has more advantages in improving the pregnancy rate of PCOS, and it also can reduce the adverse reactions of Clomiphene alone. Acupuncture & Moxibustion can be used as a recommended treatment for PCOS. More cases should also be included in the subgroup analysis to study the impact of Acupuncture & Moxibustion programs on clinical efficacy and further optimize the Acupuncture & Moxibustion treatment program. https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier (CRD42023433057).

Chinese Medicine Sequential Therapy Improves Pregnancy Outcomes after Surgery for Endometriosis-Associated Infertility: A Multicenter Randomized Double-blind Placebo Parallel Controlled Clinical Trial

To evaluate the efficacy and safety of Chinese medicine (CM) improving pregnancy outcomes after surgery for endometriosis-associated infertility. A multicenter, randomized, double-blind placebo parallel controlled clinical trial was designed. A total of 202 patients who had laparoscopy for endometriosis-associated infertility with qi stagnation and blood stasis syndrome were included and randomly divided into the CM treatment group and placebo control group at a ratio of 1:1 using a central block randomization from May 2014 to September 2017, 101 patients in each group. The two groups received continuous intervention at 1-5 days after surgery, for 6 menstrual cycles. Before ovulation, the CM group was treated Huoxue Xiaoyi Granule (); after ovulation, Bushen Zhuyun Granule ( was involved. The control group was treated with placebo. Transvaginal ultrasonography was performed every menstrual cycle during the treatment, and female hormone levels in the follicular and luteal phases were measured during the 1st, 3rd and 6th menstrual cycles. The analysis was continued until pregnancy. The primary outcomes were clinical pregnancy rate and pregnancy outcome, and the secondary outcomes were follicular development and endometrial receptivity. Safety evaluations were performed before and after treatment. (1) Clinical pregnancy and live birth rates: the clinical pregnancy and live birth rates of the CM group were significantly higher than those of the placebo group [44.6% (45/101) vs. 29.7% (30/101), 34.7% (35/101) vs. 20.8% (21/101), both P<0.05]. (2) Follicle development: the incidence of dominant follicles, rate of cumulative cycle ovulation, and rate of cumulative cycle mature follicle ovulation were significantly higher in the CM group than those in the placebo group [93.8% (350/373) vs. 89.5% (341/381), 80.4% (275/342) vs. 69.1% (253/366), 65.8% (181/275) vs 56.1% (142/253), P<0.05 or P<0.01]). The incidence of cumulative cycle luteinized unruptured follicle syndrome was significantly lower in the CM group than in the placebo group [11.7% (40/342) vs. 17.8% (65/366), P<0.05). (3) Endometrial receptivity: after treatment, both endometrial types and endometrial blood flow types in the CM group were mainly types A and B, while those in the placebo group were mainly types B and C, with a significant difference between the two groups (both P<0.05). (4) Adverse events: the incidence of adverse events between the two groups was not significantly different (P>0.05). Strategies for activating blood circulation-regulating Gan (Liver)-tonifying Shen (Kidney) sequential therapy can effectively improve the clinical pregnancy rate and live birth rate of endometriosis-associated infertility with qi stagnation and blood stasis after laparoscopy, improve follicular development, promote ovulation, improve endometrial receptivity, while being a safe treatment option. (Trial registration No. NCT02676713).

Injection of human chorionic gonadotropin (hCG) can cause the luteinized unruptured follicle syndrome

Purpose: To demonstrate that the injection of human chorionic gonadotropin (hCG) intramuscularly for purpose of timing of an intrauterine insemination (IUI) can cause an oocyte to fail to rupture from the follicle. Materials and Methods: A 33-year-old woman sought help for infertility that seemed related to a male factor problem. The office performed IUI’s morning and evenings on weekdays but only in the morning on weekends. The timing of IUI was generally 40 to 48 hours after the initiation of the luteinizing hormone (LH) surge. When a follicle reached a minimum E2 of 200 pg/mL and an ultrasound with at least one follicle of an average of 20 mm, an injection of hCG 10,000 units I.M. was given in the evening on a Thursday or Friday, for an IUI on Saturday or Sunday. Weekday IUI’s were based on endogenous LH surge. Ultrasounds were performed on the day of IUI and the next day, if no oocyte was released. Release was considered to have occurred if shrinkage of the follicle by &gt;5 mm took place without the serum P exceeded 2 ng/dL. Results: In six natural cycles where IUI was performed Monday-Friday, the peak sera E2 levels reached 368, 334, 337, 465, 365, and 355 pg/mL. Oocyte release was confirmed in all six cycles. There were two cycles where hCG was given for weekend IUI’s. In neither cycle was oocyte release demonstrated. Leuprolide acetate also failed to cause oocyte release. Discussion: Though hCG injection and GnRH agonists can correct the luteinized unruptured follicle (LUF) syndrome, in some instances, hCG and GnRH agonists can actually cause LUF syndrome.

Non-steroidal anti-inflammatory drug induces luteinized unruptured follicle syndrome in young female juvenile idiopathic arthritis patients.

To assess prospectively luteinized unruptured follicle (LUF) syndrome in juvenile idiopathic arthritis (JIA) patients with and without non-steroidal anti-inflammatory drugs (NSAIDs) and healthy controls. Twenty-three adolescent and young adult female JIA patients (ILAR criteria) and 11 female healthy subjects were studied by pelvic ultrasound monitoring for follicular development and ovulation in one menstrual cycle. LUF syndrome was prospectively investigated by pelvic ultrasound with a dominant ovarian follicle without signs of follicular rupture, with elevation of serum progesterone in the luteal phase of the menstrual cycle and luteinizing hormone (LH) detected in the urine. Comparison between JIA patients with (n = 8) vs. without NSAIDs (n = 15) and healthy controls (n = 11) revealed that LUF syndrome was significantly higher in the former group (2 (25%) vs. 0% vs. 0%, p = 0.049). These two patients with LUF syndrome had normal menstrual cycles without reduced ovarian reserve, and they were under naproxen 500mg bid during the menstrual cycle. Disease duration was comparable in JIA with and without NSAIDs [19.8 (4.4-25) vs. 13 (3.1-33) years, p = 0.232]. Further comparison between JIA patients with and without NSAIDs and healthy controls showed similar mean anti-Müllerian hormone levels (p = 0.909), estradiol (p = 0.436), FSH (p = 0.662), LH (p = 0.686), and mean antral follicle count (p = 0.240) and ovarian volume (p = 0.363). No differences were evidenced in three groups regarding Caucasian race, body mass index, duration, and length of menstrual cycles (p > 0.05). This is the first study to identify that JIA patients have a high frequency of LUF without impaired ovarian reserve. Future prospective studies are necessary to determine if chronic/continuous use of NSAIDs in JIA will have an impact in these patients' fertility.

The role of acupuncture-moxibustion in ovulation induction based on the Chinese Medicine and Acupuncture-moxibustion Databank

Ovulatory dysfunction refers to absent ovulation or luteal insufficiency. It is commonly seen in women with irregular menstruation or menstrual cycles, especially in those with oligomenorrhea or amenorrhea. Ovulatory dysfunction is considered the single-most frequent cause of female infertility. Clinically, the two major causes of ovulatory dysfunction are polycystic ovarian syndrome (PCOS) and luteinized unruptured follicle syndrome (LUFS). Acupuncture-moxibustion improves ovulation and helps with infertility. Through a systematic review and analysis on relevant literatures in Chinese Medicine and Acupuncture-moxibustion Databank over the last decade, this paper summarized the characteristics and pattern of acupuncture-moxibustion points for improving ovulation in order to provide an optimal acupuncture-moxibustion protocol in this regard.

Chinese herbal medicine for subfertile women with polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is one of the most common reproductive endocrinology abnormalities, and affects 5% to 10% of women of reproductive age. Western medicines, such as oral contraceptives, insulin sensitizers and laparoscopic ovarian drilling (LOD), have been used to treat PCOS. Recently, many studies have been published that consider Chinese herbal medicine (CHM) as an alternative treatment for women with PCOS. To assess the efficacy and safety of CHM for subfertile women with PCOS. We searched sources, including the following databases, from inception to 9 June 2016: the Cochrane Gynaecology and Fertility Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Allied and Complementary Medicine (AMED), PsycINFO, Chinese National Knowledge Infrastructure (CNKI), VIP, Wanfang and trial registries. In addition, we searched the reference lists of included trials and contacted experts in the field to locate trials. Randomized controlled trials (RCTs) that considered the use of CHM for the treatment of subfertile women with PCOS. Two review authors independently screened appropriate trials for inclusion, assessed the risk of bias in included studies and extracted data. We contacted primary study authors for additional information. We conducted meta-analyses. We used the odds ratios (ORs) to report dichotomous data, with 95% confidence intervals (CI). We assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. We included five RCTs with 414 participants. The comparisons in the included trials were as follows: CHM versus clomiphene, CHM plus clomiphene versus clomiphene (with or without ethinyloestradiol cyproterone acetate (CEA)), CHM plus follicle aspiration plus ovulation induction versus follicle aspiration plus ovulation induction alone, and CHM plus laparoscopic ovarian drilling (LOD) versus LOD alone. The overall quality of the evidence for most comparisons was very low.None of the included studies reported live birth rate, and only one study reported data on adverse events.When CHM was compared with clomiphene (with or without LOD in both arms), there was no evidence of a difference between the groups in pregnancy rates (odds ratio (OR) 1.98, 95% confidence interval (CI) 0.78 to 5.06; two studies, 90 participants, I² statistic = 0%, very low quality evidence). No study reported data on adverse events. When CHM plus clomiphene was compared with clomiphene (with or without CEA), there was low quality evidence of a higher pregnancy rate in the CHM plus clomiphene group (OR 2.62, 95% CI 1.65 to 4.14; three RCTs, 300 women, I² statistic = 0%,low quality evidence). No data were reported on adverse events.When CHM with follicle aspiration and ovulation induction was compared with follicle aspiration and ovulation induction alone, there was no evidence of a difference between the groups in pregnancy rates (OR 1.60, 95% CI 0.46 to 5.52; one study, 44 women, very low quality evidence), severe luteinized unruptured follicle syndrome (LUFS) (OR 0.60, 95% CI 0.06 to 6.14; one study, 44 women, very low quality evidence), ovarian hyperstimulation syndrome (OHSS) (OR 0.16, 95% CI 0.00 to 8.19; one study, 44 women, very low quality evidence) or multiple pregnancy (OR 0.60, 95% CI 0.06 to 6.14; one study, 44 women, very low quality evidence).When CHM with LOD was compared with LOD alone, there was no evidence of a difference between the groups in rates of pregnancy (OR 3.50, 95% CI 0.72 to 17.09; one study, 30 women, very low quality evidence), No data were reported on adverse events.There was no evidence of a difference between any of the comparison groups for any other outcomes. The quality of the evidence for all other comparisons and outcomes was very low. The main limitations in the evidence were failure to report live birth or adverse events, failure to describe study methods in adequate detail and imprecision due to very low event rates and wide CIs. There is insufficient evidence to support the use of CHM for women with PCOS and subfertility. No data are available on live birth, and there is no consistent evidence to indicate that CHM influences fertility outcomes. However there is very limited low quality evidence to suggest that the addition of CHM to clomiphene may improve pregnancy rates. There is insufficient evidence on adverse effects to indicate whether CHM is safe.

The mare as a model for luteinized unruptured follicle syndrome: intrafollicular endocrine milieu.

Luteinized unruptured follicle (LUF) syndrome is a recurrent anovulatory dysfunction that affects up to 23% of women with normal menstrual cycles and up to 73% with endometriosis. Mechanisms underlying the development of LUF syndrome in mares were studied to provide a potential model for human anovulation. The effect of extended increase in circulating LH achieved by administration of recombinant equine LH (reLH) or a short surge of LH and decrease in progesterone induced by prostaglandin F2α (PGF2α) on LUF formation (Experiment 1), identification of an optimal dose of COX-2 inhibitor (flunixin meglumine, FM; to block the effect of prostaglandins) for inducing LUFs (Experiment 2), and evaluation of intrafollicular endocrine milieu in LUFs (Experiment 3) were investigated. In Experiment 1, mares were treated with reLH from Day 7 to Day 15 (Day 0=ovulation), PGF2α on Day 7, or in combination. In Experiment 2, FM at doses of 2.0 or 3.0 mg/kg every 12 h and human chorionic gonadotropin (hCG) (1500 IU) were administered after a follicle ≥32 mm was detected. In Experiment 3, FM at a dose of 2.0 mg/kg every 12 h plus hCG was used to induce LUFs and investigate the intrafollicular endocrine milieu. No LUFs were induced by reLH or PGF2α treatment; however, LUFs were induced in 100% of mares using FM. Intrafollicular PGF2α metabolite, PGF2α, and PGE2 were lower and the ratio of PGE2:PGF2α was higher in the induced LUF group. Higher levels of intrafollicular E2 and total primary sex steroids were observed in the induced LUF group along with a tendency for higher levels of GH, cortisol, and T; however, LH, PRL, VEGF-A, and NO did not differ between groups. In conclusion, this study reveals part of the intrafollicular endocrine milieu and the association of prostaglandins in LUF formation, and indicates that the mare might be an appropriate model for studying the poorly understood LUF syndrome.

253 THE MARE MODEL FOR LUTEINIZED UNRUPTURED FOLLICLE SYNDROME: INTRAFOLLICULAR ENDOCRINE MILIEU

Mechanisms underlying the development of luteinized unruptured follicle (LUF) syndrome in mares were studied to provide a model for human anovulation. The aims of the present study were (1) to determine the effect of recombinant equine LH (reLH) and prostaglandin F2α (PGF2α) on LUF formation (Experiment 1), (2) to identify an optimal dose of COX-2 inhibitor (flunixin-meglumine; FM) required to experimentally induce LUF (Experiment 2), and (3) to evaluate the intrafollicular endocrine milieu in induced LUF (Experiment 3). In Experiment 1, mares (n = 30) were treated with reLH from Days 7 to 15 (Day 0 = ovulation), with PGF2α on Day 7 or in combination. In Experiment 2 (n = 18 mares), FM at doses of 2.0 or 3.0 mg kg–1 every 12 h and hCG (1500 IU) were administered after a follicle ≥32 mm was detected. In Experiment 3 (n = 23 mares), FM at a dose of 2.0 mg kg–1 every 12 h plus hCG was used to induce LUF and investigate the intrafollicular endocrine milieu. Shapiro-Wilk tests were used for analysing data for normal distribution, and data not normally distributed were transformed to ranks before any further analyses. For sequential data, mixed model repeated-measures ANOVA were used. For single-point data, Student’s t-tests were used. No LUF were induced in mares treated with reLH or PGF2α, in combination or separately. However, LUF were induced in 100% of mares using FM at the dose rate of 2.0 and 3.0 mg kg–1 of body weight in combination with 1500 IU of hCG. Intrafollicular PGF2α metabolite (PGFM), PGF2α, and prostaglandin E2 (PGE2) were lower, and the ratio of PGE2 : PGF2α was higher in induced LUF. Higher levels of intrafollicular growth hormone, cortisol, oestradiol, testosterone, and total primary sex steroids were observed in the induced LUF group; however, LH, prolactin, vascular endothelial growth factor-A, and nitric oxide did not differ between the control and induced LUF groups. In conclusion, COX-2 inhibitors used in conjunction with hCG can be used to pharmacologically induce LUF with 100% success in mares. This study revealed part of the intrafollicular endocrine milieu and the association of prostaglandins in LUF formation. We postulated that LUF result from decreased intrafollicular prostaglandin concentrations or altered prostaglandin synthesis, as indicated by disparity in PGE2 : PGF2α ratio. Increased intrafollicular oestradiol, testosterone, cortisol, and growth hormone were associated with LUF formation; however, further studies are necessary to ascertain the cause-effect relationship. The effect of LH on LUF formation remains unclear. This study further encourages the use of intrafollicular v. systemic biomarkers for evaluating ovulatory disorders. Finally, results from this study support the use of the mare as a model for investigating the poorly understood LUF syndrome in women.

Review on studies of acupuncture treatment for luteinized unruptured follicle syndrome

Luteinized unruptured follicle syndrome (LUFS), a specific type of ovulation disorder, is for a cause of female infertility. Acupuncture therapy has a good effect for LUFS. In order to understand the clinical effects and research situation of acupuncture therapy for LUFS, the author analyzed and reviewed the relevant literature. It was indicated by the findings that acupuncture therapy and integrative therapy of acupuncture and Chinese herbs have good therapeutic effect for this disease. Acupuncture therapy has the effect to promote ovulation. By the therapeutic principle to tonify the kidney and circulate blood, acupuncture therapy mostly was adopted in the period of ovulation. The acupoints are mostly selected from the lower abdomen and lower limbs, possibly based upon syndrome differentiation at the same time. The needling techniques are of certain characteristics. But, the issues of low quality, un-standardized inclusive, exclusive criteria and effective criteria still exist in the current clinical study.

Granulocyte colony-stimulating factor as a potential inducer of ovulation in infertile women with luteinized unruptured follicle syndrome

Luteinized unruptured follicle (LUF) syndrome is one of the intractable ovulation disorders that are commonly observed during cycles of treatment with ovulation inducers, for which no effective therapy other than assisted reproductive technology is available. Here, we investigated whether granulocyte colony-stimulating factor (G-CSF) could prevent the onset of LUF syndrome. We analyzed the effects of G-CSF in 68 infertile women with LUF syndrome who received ovulation induction (clomiphene + human chorionic gonadotropin [hCG] therapy or follicle-stimulating hormone + hCG therapy). G-CSF (lenograstim, 100 μg) was administered subcutaneously. Onsets of LUF syndrome were compared between the cycle during which G-CSF was given in combination with the ovulation inducer (ie, the G-CSF treatment cycle) and the subsequent cycle during which only the ovulation inducer was given (ie, the G-CSF nontreatment control cycle). The results showed that LUF syndrome recurred in only 3 cycles during the G-CSF treatment cycle (4.4% [3/68 cycles]), whereas LUF syndrome recurred in 13 cycles during the subsequent G-CSF nontreatment control cycle (19.1% [13/68 cycles]). The additional use of G-CSF significantly prevented the onset of LUF syndrome during ovulation induction (P = 0.013, McNemar test). No serious adverse reactions because of the administration of G-CSF were observed. In conclusion, our findings indicate that G-CSF may become a useful therapy for LUF syndrome.

Effects of Letrozole-HMG and Clomiphene-HMG on Incidence of Luteinized Unruptured Follicle Syndrome in Infertile Women Undergoing Induction Ovulation and Intrauterine Insemination: A Randomised Trial.

Background:Luteinized unruptured follicle (LUF) syndrome is considered a cause of ovulation failure and a subtle cause of infertility. Preovulatory injection of human chorionic gonadotropin (HCG) prevents or treats LUF syndrome, but it has also occurred after the induction of ovulation with clomiphene/HMG and HCG. This study was designed for evaluation and comparison of LUF incidence in eligible infertile women undergoing two stimulation protocols (clomiphene + HMG and letrozole + HMG) in addition to intrauterine insemination (IUI). Some related factors were compared between LUF and non-LUF cycles as secondary outcomes.Methods:The study was designed as a prospective randomized controlled trial. Patients were randomized using a table of random numbers into two equal protocol groups. For group A, (n = 90) clomiphene citrate was administrated orally in doses of 100 mg/day, and group B (n = 90) orally received letrozole 5 mg/day from day 3 to 7 of the menstrual cycle. Then HMG 75IU/day was administered intramuscularly in both groups on day 8 of the menstrual cycle and the dose was adjusted on the basis of ovarian response. The optimum size of preovulatory follicles for the injection of HCG (10,000 IU) was considered 18–23 mm. The number and size of preovulatory follicles were assessed by vaginal ultrasound 12 h before HCG (D0). Endometrial thickness was measured as well. IUI was performed on all patients 38–40 h after HCG. The second ultrasound examination was performed to observe the evidence of oocyte releasing at the time of IUI (D1). If the follicles were unruptured, a third sonography was performed on day 7 after HCG (D7) to observe LUF syndrome.Results:There was a significant difference between clomiphene-HMG and letrozole-HMG in LUF (p = 0.021) and pregnancy (p = 0.041). The complete LUF in letrozole-HMG was lower than the alternative group and the pregnancy rate was higher. The patients in the non-LUF group had higher midluteal progesterone and a thicker endometrium compared to LUF cycles (p = 0.039) and (p < 0.001). The results of our multivariate logistic regression indicate that size 18–19.9 mm leads to the complete LUF less than ≥22 mm [AOR: 0.25, P = 0.005], and in size 20– 21.9 mm as well [AOR: 0.17, P = 0.002].Conclusion:Letrozole, with lower incidences of LUF, is more effective than clomiphene citrate for the induction of ovulation in IUI cycles. In our study, we illustrated that larger follicles of ≥22 mm diameter were associated with higher incidences of LUF. We recommend that further studies investigate and focus on the relationship between follicular size and/or full hormonal profiles and LUF.

Preliminary study on relationship of disease-syndrome-symptom of ovulatory disorder infertility based on factor analysis

In this study, the clinical data of 240 cases of data acquisition on ovulation in patients with anovulatory infertility. Using the method of factor analysis, summed up the distribution situation of various syndromes and the relationship of disease-syndrome-symptom. From the study we found that polycystic ocary syndrome > premature ovarian failure > corpus luteum insufficiency > luteinized unruptured follicle syndrome > hyperprolactinemia > anovulatory dysfunctional uterine bleeding. Using the factor analysis method, the syndromes of anovulatory infertility were divided into six types and the distribution proportion of them is: kidney Yang deficiency and blood stasis > kidney Yang deficiency > kidney Yin deficiency and blood stasis > kidney Yin deficiency and liver Qi stagnation syndrome > kidney Yang deficiency and phlegm dampness stagnation > kidney Yin deficiency. By means of statistics, the traditional Chinese medicine (TCM) symptoms as abdomen pain before menstrual onset, obfuscation colour, cold lower abdomen, insomnia, fatigue, eyes dark, face dark or ring lip dark, before and after menstruation breast swelling, chest tightness, irritable insomnia, depression and lower abdomen pain during menstruation etc contribute high degree in the process. Polycystic ovary syndrome and premature are the main causes of ovulatory disorder infertility and the disease incidence rate assumed the tendency which rose year by year. The treatment of the disease of kidney yang deficiency syndrome scales biggest the disease degree of contribution. Blood stasis is the important factor in the process of pathogenesis evolution. In the study of disease distribution, we found that symptom distribution trend roughly the same and the same symptom severity in different diseases with different, which provides experience for the theory-different diseases with the same therapeutic method. These conclusions provide guidance and reference evidences for clinic practice.

Effect of sex hormone levels on ovulation induction outcome

Objective To discuss the influence of sex hormone levels on ovulation outcome during different periods in both luteinized unruptured follicle syndrome (LUFS) cycle patients and normal ovulatory cycle patients.Methods Treating the infertile women with ovulatory dysfunction by taking CC+HCG,the levels of the serum follicle stimulating hormone (FSH),Luteinizing hormone (LH),estradiol (E2),progesterone (P),prolactin (PRL),testosterone (T) were measured respectively on the 3rd day (C3),the 10th day (C10),follicle maturity day (CM).Ovulation was surveyed with transvaginal ultrasonography (TVS) at the same time.Group A was defined as ovulation after induced ovulation while group B was defined as LUFS after induced ovulation.Results The levels of E2 and P on C3 day,FSH on C 10 day,LH on CM day of group B were all significantly lower than those of group A (P＜0.05).Conclusion Sex hormones play very important roles in LUFS occurring. Key words: Ovulation induction; Sex hormone; CC; HCG

Luteinized unruptured follicle syndrome increased by inactive disease and selective cyclooxygenase 2 inhibitors in women with inflammatory arthropathies

Administration of nonsteroidal antiinflammatory drugs (NSAIDs) may impair fertility. The occurrence of the luteinized unruptured follicle (LUF) syndrome was assessed in women with inflammatory arthropathies exposed to NSAIDs and compared to that in nonexposed women. Fourteen patients with inflammatory rheumatic disease, 29 women with noninflammatory musculoskeletal conditions, and 449 women not exposed to NSAIDs were studied by intravaginal ultrasound monitoring for follicular development and ovulation in 1 or more menstrual cycles. Disease activity was assessed in inflammatory rheumatic disease. In 59 monitored cycles of patients with continuous NSAID exposure, 35.6% of LUF syndromes occurred compared to 3.4% of LUF syndromes in untreated women (P < 0.001). Etoricoxib was responsible for 75% of LUF syndromes in patients exposed continuously, whereas diclofenac generated 15% of LUF syndromes. An ibuprofen dosage of 1,600 mg/day did not induce LUF syndrome either at continuous periovulatory or discontinuous exposure. Interestingly, the frequency of LUF syndrome was 46.2% in patients with inactive inflammatory disease compared to 15% in patients with active disease (P = 0.023). Etoricoxib generated LUF syndrome in 94.2% of the cases with inactive disease versus 28.6% in patients with active disease (P = 0.003). NSAIDs increased the risk of the LUF syndrome, particularly in patients with inactive disease. The selective cyclooxygenase 2 (COX-2) inhibitor etoricoxib was a more potent inductor of LUF syndrome than nonselective COX inhibitors. Continuous periovulatory exposure to NSAIDs should be avoided when planning a pregnancy in patients with rheumatic diseases.

Clinical observations on electroacupuncture-induced ovulation in patients with luteinized unruptured follicle syndrome

Objective: To investigate the curative effect of electroacupuncture on luteinized unruptured follicle syndrome(LUFS) and its mechanism.

AC-012 Clinical research on luteinized unruptured follicle syndrome (LUFS) treated with electric acupuncture

AC-012 Clinical research on luteinized unruptured follicle syndrome (LUFS) treated with electric acupuncture

Increased Incidence and Recurrence of Recent Corpus Luteum Without Ovulation Stigma (Luteinized Unruptured Follicle Syndrome?) in Baboons With Endometriosis

To test the hypothesis that a recent corpus luteum (CL) without fresh ovulation stigma (OS) can be found with a higher incidence and recurrence in baboons with endometriosis and is associated with a reduced egg recovery rate after uterine flush. One hundred thirty-eight laparoscopies were performed in the early luteal phase of 52 cycles in 32 female baboons with a normal pelvis (controls) and of 86 cycles in 21 animals with endometriosis. The incidence and recurrence of a recent CL without OS was studied during each laparoscopy and during the first three laparoscopies in 15 baboons (five controls, ten with endometriosis), respectively. The association between the presence of a recent CL without OS and the egg recovery rate was evaluated during 65 cycles in 21 baboons after uterine flush. When all 138 laparoscopies were analyzed, the incidence of a recent CL without OS was higher (P < .03) in animals with stage II-IV endometriosis (35%) than in those with stage I disease (19%) or controls (11%). Both the incidence (seven of ten) and recurrence (three of ten) of a recent CL without OS were higher in baboons with endometriosis than in controls (zero of five, P < .02) when studied during the first three laparoscopies. Laparoscopies in primates having a recent CL without OS were associated with a lower egg recovery rate (13%) than in animals with recent CL and OS (54%, P = .005). A recent CL without OS was associated with a reduced egg recovery rate and could be found with a higher incidence and recurrence in baboons with endometriosis than in controls, suggesting that luteinized unruptured follicle syndrome exists and could contribute to endometriosis-associated subfertility.

Complete and partial luteinized unruptured follicle syndrome after ovarian stimulation with clomiphene citrate/human menopausal gonadotrophin/human chorionic gonadotrophin

A total of 31 clomiphene citrate/human menopausal gonadotrophin (HMG)/human chorionic gonadotrophin (HCG)-stimulated cycles in 28 patients were investigated to determine the fate of each of the matured follicles. A standard stimulation regimen was adhered to, and ultrasound as well as hormonal monitoring was performed. All follicles were measured by vaginal ultrasound at -12, +35 and +45 h relative to HCG administration and at 7 days after HCG administration. Of the 220 follicles, 107 (48.6%) ruptured. The number of ruptured follicles per cycle was correlated with the mid-luteal progesterone concentration (r = 0.63, P = 0.0005). The probability of follicular rupture was related to follicular diameter at 12 h before HCG administration; 6% of follicles < 12 mm in diameter ruptured compared with 87% of follicles 18-19 mm. A complete luteinized unruptured follicle (LUF) syndrome was observed in six cycles (20%). In these cycles, follicular growth and oestradiol, progesterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations at 12 h before HCG administration were similar to those in cycles with follicular rupture. However, mid-luteal progesterone concentrations were lower in complete LUF cycles (46.97 +/- 8.95 nmol/l versus 108.74 +/- 12.27 nmol/l; P = 0.02). These data demonstrate that in stimulated cycles many follicles, usually the smaller ones, fail to rupture, even after HCG administration. Complete LUF syndrome, despite a strong exogenous ovulatory signal, and the absence of any difference in peri-ovulatory hormonal parameters, indicates that the defect causing LUF resides in the follicle itself and/or hormonal changes during the follicular phase.