Luteinized Unruptured Follicle Research Articles

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 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.

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.

A prospective, randomized, pharmacodynamic study of quick-starting a desogestrel progestin-only pill following ulipristal acetate for emergency contraception.

Is there a pharmacodynamic interaction between ulipristal acetate (UPA) 30 mg for emergency contraception and a daily progestin-only contraceptive pill, desogestrel (DSG) 0.75 mg, when initiated the next day? In this study, DSG impaired the ability of UPA to delay ovulation, but UPA had little impact on the onset of contraceptive effects due to DSG. UPA is a progesterone receptor modulator used for emergency contraceptive (EC) at the dose of 30 mg. UPA delays ovulation by at least 5 days when administered in the mid to late follicular phase. In theory, potent progestins could reactivate progesterone signaling that leads to follicle rupture, thereby impacting the effectiveness of UPA as EC. In addition, UPA could alter the onset of the contraceptive effect of progestin-containing contraceptives started immediately after UPA. A single-blind (for observer), placebo-controlled, partial crossover study was conducted in two sites [Dominican Republic (DR) and the Netherlands (NDL)] over 11 months from October 2012 to September 2013. Healthy female volunteers participated in two of the three treatment cycles separated by a washout cycle. Treatment combinations studied were as follows: (i) a single 30 mg dose of UPA followed by 75 µg per day DSG for 20 days, (ii) a single 30 mg dose of UPA followed by 20 days of placebo matching that of DSG (PLB2) or (iii) one tablet of placebo-matching UPA (PLB1) followed by 75 µg per day DSG for 20 days. Participants were randomized to one of the three treatment sequences (UPA + DSG/UPA + PLB2, PLB1 + DSG/UPA + DSG and UPA + PLB2/PLB1 + DSG) when a lead follicle was ≥ 14 to <16 mm diameter on transvaginal ultrasound imaging (TVU). A total of 71 women were included, and 49 were randomized to a first treatment combination of the three period sequences (20 in the DR and 29 in the NDL); 41 of the 49 continued and completed two treatment combinations (20 in the DR and 21 in the NDL). Initiating DSG treatment the day after UPA significantly reduced the ovulation delaying effect of UPA (P = 0.0054). While ovulation occurred in only one of the 29 UPA-only cycles (3%) in the first 5 days, it occurred in 13 of the 29 (45%) UPA + DSG cycles. This was a small, descriptive, pharmacodynamic study in which some findings differed by study site. Distinguishing between a cystic corpus luteum and a luteinized unruptured follicle (LUF) by TVU was difficult in some cases; however, the investigators reached consensus, when the study was still blinded, regarding ovulation based on hormone levels and careful review of daily TVU images. Initiating the use of a DSG progestin-only pill (POP) immediately after UPA reduces the ability of UPA to delay ovulation and thus may decrease its efficacy as EC. If starting a DSG POP after using UPA for EC, and possibly any progestin-only method, consideration should be given to delaying for at least 5 days after UPA intake in order to preserve the ovulation delaying effects of UPA.

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.

The history and current status of anti-sperm antibody research

we have studied the implication of bone morphogenetic proteins (BMP) in the ovarian physiology. In the present study,weexhibit ourdata regarding (1) folliculogenesis, (2) ovulation and (3) polycystic ovary syndrome (PCOS), especially from the point of the relationship between ovarian cells and immune-competent cells. Folliculogenesis:Although the formation of an individual capillary network in the theca cell layer is required for ovarian folliculogenesis, the mechanism has not been clarified. We found that theca cell derived BMP-7 stimulated VEGF secretion levels in GC significantly. In endothelial cells, BMP-7 increased the cell number and induced VEGF receptor mRNA. BMP-7 might work to form vasculature around follicles via induction of VEGF expression in GC and increased sensitivity of endothelial cells to VEGF. Ovulation: As granulocyte colony-stimulating factor (G-CSF) is known to be a candidate for a treatment of luteinized unruptured follicle (LUF), neutrophils might be involved in ovulatory process. BMP cytokine is known to regulate ovulation, as BMP-6 null mice exhibit a decrease in the number of ovulatory follicleswithout effect on either themorphology or the dynamics of follicular development. We found that BMP-6 significantly increased growthregulated oncogene (GRO)levels in human GC. On the other hand, BMP-6 suppressed the relative expression of the protease inhibitors, secretory leukocyte peptidase inhibitor (SLPI) in GC. BMP-6 might play a role in ovulation by increasing the accumulation of neutrophils in the ovulatory follicle and suppressing the effect of protease inhibitor. PCOS: Plasminogen activator inhibitor-1 (PAI-1), the main physiological inhibitor of plasminogen activation, is elevated in women with PCOS and has been linked to PCOS in a mouse model of the disease. We have found that TGFand TNFwhich are involved in the etiology of PCOS, increased PAI-1 secretion levels by cultured GC. Insulin sensitizing drugs suppressed TGFand TNFmRNA expression in peritoneal fluid mononuclear cells. Our data suggested that insulin sensitizing agentsmayprovide a potential therapy for PCOS via down regulation of PAI-1 expression indirectly. To understand the etiology of PCOS, the regulation of immune-competent cells should be taken into consideration.

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.

The Effect of Sulpiride Treatment During the Periovulatory Period on Prolactin Concentration and Ovulation in the Mare

Sixteen estrous cycles from 10 cyclic mares were randomly assigned to a control or sulpiride group (n = 8 each). All mares received 1,500 IU of human chorionic gonadotropin (hCG) (hour 0) during estrus with a follicular diameter ≥32 mm. Mares were scanned every 12 hours until ovulation. In the treatment group, beginning at hour 0, each mare received 1.5 mg/kg of sulpiride every 12 hours intra-muscularly until ovulation or formation of a luteinized unruptured follicle (LUF). Concentrations of luteinizing hormone (LH) and prolactin (PRL) were measured by radioimmunoassay. In each group, there were 10 preovulatory follicles for the eight cycles. The ovulation rate (9/10, 90%) was similar in the control and sulpiride groups. Two mares formed an LUF, which was first detected at hours 48 and 72 for the sulpiride and control mares, respectively. The interval from hCG to ovulation was 49.5 ± 11.1 and 43.5 ± 5.8 hours, for the control and sulpiride groups, respectively (P > .5). LH followed the typical preovulatory surge pattern, with no difference between groups (P > .5). Sulpiride administration increased PRL concentration in treated mares at 24 (P < .1), 36, and 48 hours (P < .05) after treatment. In conclusion, sulpiride administration every 12 hours increased PRL concentration in treated mares after 24 hours of the beginning of treatment. However, at this time window and concentration, PRL did not have any effect on ovulation. The control mare that developed an LUF had a PRL concentration similar to other ovulatory control mares (always ≤10 ng/mL).

Granulocyte colony-stimulating factor (G-CSF) prevents luteinized unruptured follicle (LUF) caused clomiphene treatment

To evaluate the relevance of G-CSF in ovulation, we examined whether G-CSF administration can decrease the incidence of LUF in clomiphene (CC) – hCG treatment, which is known to cause LUF at the high recurrence rate.

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.

Impact of luteinized unruptured follicles on endometrial receptivity

This study examined the impact of luteinized unruptured follicle (LUF) on endometrial receptivity. The menstrual cycle of 17 LUF patients (LUF group) and 13 ovulatory women (control group) was monitored by measuring LH level in urine and by ultrasonic examination. An endometrial biopsy at the sixth to tenth day after LH surge was taken in all the patients. The expressions of endometrial ER, PR and integrin ανβ3 were immunohistochemically determined. At the same time, the serum levels of E(2) and P were detected by chemiluminescence. The results exhibited that (1) The mean serum P level in LUF group (7.32±2.56 ng/mL) was significantly lower than that in control group (11.17±3.17 ng/mL) (P<0.01). But there was no significant difference in the mean serum E2 levels between LUF group (179.35±81.60 pg/mL) and the control group (198.58±75.23 pg/mL) (P>0.05); (2) The mean expression intensities of ER, PR in endometrium of LUF group (183.86±2.43, 167.94±3.04) were significantly higher than those in control group (109.35±6.31, 105.98±4.07) (P<0.01); (3) The mean expression intensities of integrin ανβ3 in endomtrium of LUF patients (114.90±11.38) were significantly lower than those in control group (191.34±1.82) (P<0.01); (4) The change profile of integrin ανβ3 expression in the endometrium of LUF patients was in positive relation with serum P level (r=0.77, P<0.01), but bore no significant relationship with serum E(2) level (r=0.01, P>0.05). It was concluded that the depression of serum P levels in LUF patients was closely related to the failure of the down-regulation of ER and PR, and the low expressions of integrin ανβ3 also suggested that the delayed implantation and the impaired endometrial receptivity had impact on embryonic implantation.

O941 Usefulness of G-CSF in the treatment of luteinized unruptured follicle (LUF)

International Journal of Gynecology & ObstetricsVolume 107, Issue S2 p. S360-S361 Free communication (oral) presentations O941 Usefulness of G-CSF in the treatment of luteinized unruptured follicle (LUF) H. Tomizawa, H. TomizawaSearch for more papers by this authorN. Neyatani, N. NeyataniSearch for more papers by this authorH. Takagi, H. TakagiSearch for more papers by this authorR. Fujii, R. FujiiSearch for more papers by this authorS. Makinoda, S. MakinodaSearch for more papers by this author H. Tomizawa, H. TomizawaSearch for more papers by this authorN. Neyatani, N. NeyataniSearch for more papers by this authorH. Takagi, H. TakagiSearch for more papers by this authorR. Fujii, R. FujiiSearch for more papers by this authorS. Makinoda, S. MakinodaSearch for more papers by this author First published: 20 November 2009 https://doi.org/10.1016/S0020-7292(09)61314-XAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume107, IssueS2Abstracts of XIX FIGO World Congress of Gynecology and ObstetricsOctober 2009Pages S360-S361 RelatedInformation

Effect of stimulation protocol on the risk of luteinized unruptured follicle (LUF) in polycystic ovarian syndrome (PCOS):does LUF affect luteal phase profile?

OBJECTIVE: Study effect of stimulation protocol on LUF risk & luteal phase profile in PCOS with LUF.DESIGN: Prospective observational studyMATERIALS AND METHODS: 964 cycles in 696 PCOS infertile women (cycle number range 1-3 cycles/patent) monitored by TVS and serum midluteal progesterone (MLP4) under different induction protocols: CC only (426 cycles), sequential CC-and hMG (462 cycles), and hMG only (76 cycles).Cases were started on CC .If CC resistance, anovulation or LUF occurs, sequential CC-hMG or hMG only are given next cycle. TVS monitoring was started on day -5, every other day till day + 7, the day of HCG is day 0. Ovulation was triggered by 10000 IU HCG when leading follicle reached ≥18 mm mean diameter. MLP4 was measured on day +7 Outcome measurements were ovulation (TVS evidence of follicular rupture and MLP4 ≥ 1.5 ng/mL), anovulation (failure of follicular rupture and MLP4 < 1.5 ng/mL), LUF (failure of follicular rupture with MLP4 ≥1.5 ng/mL) and pregnancy. Comparisons between group means for continuous normally distributed variables was made by t-test, and between categorical variables was made by χ tests from which the relative risk (RR 95% CI) was derived .Non parametric correlation test was done to measure correlation of nonparametric variablesRESULTS: In CC cycles, LUF incidence was 15.1% compared to 6.9% in sequential CC-hMG (RR 2.2, 95%CI 1.4- 3.2), 5.2% in hMG (RR 2.8, 95% CI 1.1-7.4).We found significant correlation between LUF incidence and use of CC protocol. Consecutive cycle stimulation is not associated with increased LUF incidence. Only 7.1 % of LUF recurred in consecutive cycles. Compared to normal ovulatory cycles LUF had significantly lower MLP4, shorter luteal phase length, and zero pregnancy rateCONCLUSIONS: Risk of LUF in PCOS is significantly increased in cycles stimulated by CC compared with sequential CC-hMG & hMG protocols and is more related to stimulation protocol than to patient type or cycle repetition. LUF cycles show more luteal phase defect and are non-conception cycles OBJECTIVE: Study effect of stimulation protocol on LUF risk & luteal phase profile in PCOS with LUF. DESIGN: Prospective observational study MATERIALS AND METHODS: 964 cycles in 696 PCOS infertile women (cycle number range 1-3 cycles/patent) monitored by TVS and serum midluteal progesterone (MLP4) under different induction protocols: CC only (426 cycles), sequential CC-and hMG (462 cycles), and hMG only (76 cycles).Cases were started on CC .If CC resistance, anovulation or LUF occurs, sequential CC-hMG or hMG only are given next cycle. TVS monitoring was started on day -5, every other day till day + 7, the day of HCG is day 0. Ovulation was triggered by 10000 IU HCG when leading follicle reached ≥18 mm mean diameter. MLP4 was measured on day +7 Outcome measurements were ovulation (TVS evidence of follicular rupture and MLP4 ≥ 1.5 ng/mL), anovulation (failure of follicular rupture and MLP4 < 1.5 ng/mL), LUF (failure of follicular rupture with MLP4 ≥1.5 ng/mL) and pregnancy. Comparisons between group means for continuous normally distributed variables was made by t-test, and between categorical variables was made by χ tests from which the relative risk (RR 95% CI) was derived .Non parametric correlation test was done to measure correlation of nonparametric variables RESULTS: In CC cycles, LUF incidence was 15.1% compared to 6.9% in sequential CC-hMG (RR 2.2, 95%CI 1.4- 3.2), 5.2% in hMG (RR 2.8, 95% CI 1.1-7.4).We found significant correlation between LUF incidence and use of CC protocol. Consecutive cycle stimulation is not associated with increased LUF incidence. Only 7.1 % of LUF recurred in consecutive cycles. Compared to normal ovulatory cycles LUF had significantly lower MLP4, shorter luteal phase length, and zero pregnancy rate CONCLUSIONS: Risk of LUF in PCOS is significantly increased in cycles stimulated by CC compared with sequential CC-hMG & hMG protocols and is more related to stimulation protocol than to patient type or cycle repetition. LUF cycles show more luteal phase defect and are non-conception cycles

Effect of luteinized unruptured follicle cycles on clinical outcomes of frozen thawed embryo transfer in Chinese women

To determine the effect of luteinized unruptured follicle (LUF) cycles on frozen thawed embryo transfer (FET). A retrospective analysis comparing the clinical outcomes after FET among 144 cases of luteinized unruptured follicle (LUF) cycles and 866 cases of ovulation cycles. Reproductive medical center, Beijing China. Chinese infertile women who underwent FET. None. Clinical pregnancy rate (PR), implantation rate. The implantation rate, clinical pregnancy rate, on-going pregnancy rate and live birth rate in LUF group were 12.76% (49/384), 27.78% (40/144), 24.31% (35/144) and 19.44% (28/144), respectively, and in ovulation group, 14.74% (332/2251), 31.29% (271/866), 28.29% (245/866) and 22.23% (193/866), respectively (p > 0.05). LUF does not affect the clinical outcomes of FET. Patients of LUF should be included in FET treatment.

Granulocyte Colony-Stimulating Factor (G-CSF) in the Mechanism of Human Ovulation and its Clinical Usefulness

In 1980, Espey proposed a famous hypothesis that mammalian ovulation is comparable to an inflammatory reaction and many researches have proved the validity of his hypothesis in the last three decades. For example, interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)- alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) and other inflammatory cytokines presence was proven in the preovulatory follicle. Since granulocyte is the major leukocyte and it plays a very important role during inflammation, the importance of granulocyte and its related cytokine, granulocyte colony-stimulating factor (G-CSF) in the mechanism of human ovulation is easily predictable. G-CSF is one of the hemopoietic cytokines and it has strong positive effects on granulocytes. G-CSF increases the number of granulocytes and it improves the function of granulocytes. In this review, the participation of leukocytes in the ovulation mechanism is demonstrated first. Second, the participation of G-CSF is shown in comparison with the above mentioned cytokines. Finally, since G-CSF has been used for more than 20 years as a medicine without severe side effects in the field of oncology, the clinical application of G-CSF for the treatment of an ovulation disorder, luteinized unruptured follicle (LUF), will be discussed.

Changes in blood-flow impedance of the human corpus luteum throughout the luteal phase and during early pregnancy

To examine changes in blood flow in the corpus luteum throughout the luteal phase and during early pregnancy. Longitudinal and cross-sectional prospective studies. University hospital and city general hospital. Sixty-one women with normal menstrual cycles and normal luteal function, 13 women with hCG-induced ovulatory cycle, 10 women with luteal phase defect, six women with luteinized unruptured follicle (LUF), and 17 pregnant women (4-10 weeks of gestation). Blood-flow impedance in the corpus luteum was assessed by transvaginal color-pulsed Doppler ultrasound. Resistance index (RI) in the corpus luteum. In the normal menstrual cycle, the RI of the preovulatory follicle was high and significantly decreased after ovulation. Luteal-RI further decreased during the early to midluteal phase but significantly increased during the late luteal phase. Those changes in luteal-RI were similar to those of the hCG-induced ovulatory cycle. Luteal-RI during the midluteal phase was significantly higher in the patients with luteal phase defect than in women with normal luteal function. Luteal-RI of the LUF patients remained high throughout the luteal phase. In pregnant women, luteal-RI remained at the midluteal phase level until 7 weeks of gestation and significantly increased thereafter. The change in luteal-RI was associated with corpus luteum development and corpus luteum regression. Luteal-RI was closely associated with luteal function.

Luteinized unruptured follicle syndrome: incidence and recurrence rate in infertile women with unexplained infertility undergoing intrauterine insemination

The objective of this study was to determine the incidence and recurrence rate of luteinized unruptured follicle (LUF) syndrome in women with unexplained infertility undergoing intrauterine insemination (IUI). A total of 167 women with unexplained infertility who underwent 292 cycles of IUI were enrolled in the study. All patients were treated with clomiphene citrate, 50-150 mg/daily from day 5 to 9 of their menstrual cycle. Ultrasound examination to confirm ovulation was performed on the day of IUI (day 0) and every day thereafter for another 3 days (days 1, 2 and 3). A total of 69 women who failed to conceive in the first cycle and 56 women who failed to conceive in the second cycle underwent second and third cycles, respectively. Of the total 167 patients who underwent first cycle, 42 (25%) had LUF. The incidence of LUF was 56.5% in 69 patients who underwent a second cycle of IUI treatment, of whom 33 patients had LUF in the first cycle with recurrence rate of 78.6%. In 56 patients who underwent 3 consecutive cycles, the incidence of LUF was 58.9% and recurrence rate of 90%. No pregnancies were recorded in patients with LUF during the study period. The incidence and recurrence rate of LUF are significantly increased in subsequent cycles of IUI. In these patients, other options of infertility treatment might be justified.