Detection Of LH Surge Research Articles

P-614 The use of home ovulation prediction kits (OPKs) in true natural cycle frozen embryo transfer (NC FET)

Abstract Study question Do urinary OPKs have inferior ability to detect the LH surge compared to daily serum monitoring among patients undergoing true NC FET? Summary answer OPKs are highly accurate and may serve as reliable tests to detect the LH surge among patients undergoing NC FET. What is known already Frozen embryo transfers continue to increase worldwide and recent evidence suggests natural cycle protocols may be superior to hormone replacement protocols because of lower risk of miscarriage and lower risk of pregnancy complications. Patients undergoing NC FET attend multiple clinic appointments which has been associated with increased patient stress levels during fertility treatment. OPKs have been found to be accurate at detecting the LH surge in the trying to conceive population and have high user acceptability. Study design, size, duration A prospective single cohort study including 139 fertility seeking participants was completed at an academic-affiliated fertility center for a duration of 12 months. Participants/materials, setting, methods Patients scheduled for NC FET (regular cycles 27-35 days, mid luteal progesterone >30 nmol/L, no luteal phase concern) with the ability to provide informed consent and access to SMS texting devices were eligible for participation. On the same day they started daily morning bloodwork as per the standard protocol (2-3 days prior to anticipated LH surge), participants began twice daily OPK testing. Upon exiting the study, patients completed a questionnaire on satisfaction with OPK use. Main results and the role of chance LH surge detection rate was 85.6% (n = 119/139) with serum monitoring and 93.5% (130/139) with OPK use (Kappa agreement 90.7%, K = 0.51, p < 0.001). Among patients with a serum-detected LH surge, OPK was positive within +/- 12 hours of the serum LH surge detection in 84.8% of patients. In 23.7% of cycles, OPK was positive the same morning as serum blood work. In 27.1% of cycles, OPK was positive 12h prior and in 33.9% of cycles, OPK was positive 12h after serum LH surge detection. Actual NC FET cycle cancellation rate was 16.6% (n = 23/139) compared to an anticipated cycle cancellation rate of 20.9% (29/139) if OPKs had been used to initiate serum monitoring. The average reduction in the number of serum monitoring visits and distance travelled in kilometers with OPK use was 3.9 visits (SD 2.1) and 155km (SD 174), respectively. The majority of participants reported satisfaction with OPK use. Of 135 patients, 110 (81.5%) strongly agreed the OPK was easy to use, 100 (74.1%) strongly agreed they would be open to using OPKs in future fertility treatments and 120 (88.9%) reported a reduction or no impact on stress levels associated with fertility treatments. Limitations, reasons for caution This study only used Clearblue Digital Ovulation Tests and the reported reliability in our study cannot be extrapolated to all OPKs. Additionally, the accuracy of the reported serum LH surge detection rate may be limited by physician specific definitions of serum LH surge. Wider implications of the findings OPKs are highly accurate and may serve as a reliable trigger for serum monitoring in NC FET. While their use would reduce the number of clinic appointments and distance travelled for patients undergoing NC FET cycles, patients should be advised OPK use may be associated with higher cycle cancellation rates. Trial registration number Not applicable

O-110 Endometrial preparation for FET: HRT vs. Natural cycle

Abstract Frozen-thawed embryo transfer (FET) cycles have increased dramatically over the past decade, mainly due to the introduction of vitrification as a more efficient method of cryopreservation, and the increase of the freeze-all strategy in order to reduce the risk of OHSS. Planning of FET cycles is a key step for the implantation of the frozen-thawed embryos since it allows the synchronization of the endometrium with the developmental stage of the embryo. Endometrial preparation can be achieved either through hormonal replacement treatment (HRT) by an artificial cycle using exogenous estrogen administration for the development of the endometrium and subsequent administration of exogenous progesterone for its secretory transformation (AC-FET) or via a natural cycle, following the detection of LH surge (NC-FET), or the trigger of ovulation with human chorionic gonadotrophin (mNC-FET). The scope of the current presentation is to provide an overview of the different methods of endometrial preparation for FET cycles, their advantages, and disadvantages, and the evidence regarding clinical but also adverse obstetrical and perinatal outcomes, following each different protocol. Trial registration number

Low progesterone levels on the day before natural cycle frozen embryo transfer are negatively associated with live birth rates.

Are progesterone (P) levels on the day before natural cycle frozen embryo transfer (NC-FET) associated with live birth rate (LBR)? Regular ovulatory women undergoing NC-FET with serum P levels <10 ng/ml on the day before blastocyst transfer have a significantly lower LBR than those with serum P levels >10 ng/ml. The importance of serum P levels around the time of embryo transfer in patients undergoing FET under artificial endometrial preparation has been well established. However, no study has analyzed the importance of serum P levels in patients undergoing FET under a true natural endometrial preparation cycle. This was a retrospective cohort study including 294 frozen blastocyst transfers under natural cycle endometrial preparation at a university-affiliated fertility centre between January 2016 and January 2019. All patients had regular menstrual cycles and underwent NC-FET with their own oocytes. Only patients who had undergone serum P measurement between 8 am and 11 am on the day before FET were included. Patients did not receive any external medication for endometrial preparation or luteal phase support. Patients were divided into two groups according to serum P levels below or above 10 ng/ml on the day before FET. Univariate analysis was carried out to describe and compare the cycle characteristics with reproductive outcomes. To evaluate the effect of P, a multivariable logistic model was fitted for each outcome after adjusting for confounding variables. Mean serum P levels on the day before FET were significantly higher in patients who had a live birth compared to those who did not (14.5 ± 7.0 vs 12.0 ± 6.6 ng/ml, 95% CI [0.83; 4.12]). The overall clinical pregnancy rate (CPR) and LBR were 42.9% and 35.4%, respectively. Patients in the higher P group (>10 ng/ml) had a higher LBR (41.1% vs 25.7%: risk difference (RD) 15.4%, 95% CI [5; 26]) and CPR (48.6% vs 33.0%: RD 15.6%, 95% CI [4; 27]). Patients with higher serum P levels on the day before FET (63% of patients) had an improved LBR (odds ratio: 1.05; 95% CI [1.02; 1.09]). Women with serum P levels <10 ng/ml on the day before FET (37% of patients) had significantly higher weights (62.5 ± 9.9 vs 58.1 ± 7.1 kg, 95% CI [1.92; 6.90]) and BMI (22.9 ± 3.6 vs 21.6 ± 2.7 kg/m2, 95% CI [0.42; 2.25]) compared to patients with P levels >10 ng/ml. The main limitation of our study is its retrospective design. Other potential limitations are the detection of LH surge through urine testing and the inclusion of patients who did and did not undergo preimplantation genetic testing for aneuploidies. The protocol used in our institution for monitoring NC-FET does not look for the onset of progesterone secretion by the corpus luteum, and a slow luteinisation process or delay of corpus luteum function cannot be ruled out. We provide evidence that a minimum serum P threshold (P >10 ng/ml) might be required for improved reproductive outcomes in NC-FET. This result suggests that there are different mechanisms by which P is produced and/or distributed by each patient. This study also provides an excellent model to evaluate the impact of luteal phase defect through NC-FET. A prospective evaluation to assess whether P supplementation should be individualised according to patient's needs is necessary to support our findings. No external funding was used, and there are no competing interests.

Correlation between Proprioception and Dynamic Postural Control during Ovulatory Phase of the Menstrual Cycle

Decreased proprioception and dynamic postural control (DPC) have been reported to be a contributing factor in anterior cruciate ligament (ACL) injuries in females. Understanding the relationship between proprioception and DPC during different phases of the menstrual cycle may provide a better understanding of gender-specific characteristics of ACL injury risk. The primary purpose of this study was to assess the relationship between DPC and both joint kinesthesia (JK) and joint position sense (JPS) in females during the ovulatory phase of the menstrual cycle. Nine moderate to highly active females. Subjects made two visits to the research facility over a two-month period. DPC, JK, and JPS were measured over two consecutive menstrual cycles during ovulatory phase (24-48 hours after LH surge detection). Joint position sense was tested using a starting angle of 90° when moving into extension, and 0° when moving into flexion. Target angles were 30°, 50°, and 70° moving into flexion, and 20°, 40°, and 60° moving into extension. Joint kinesthesia was tested moving into flexion and extension at both 15° and 45°. Moderate to high correlations were observed on six of 60 variables in the ovulatory phase of the first menstrual cycle evaluated. Although a few statistically significant correlations were identified, the clinicians may focus on those meaningful variables when they plan the rehabilitation program for prevent ACL injury. Also, while DPC deficits may increase risk of ACL injury, the data does not support that reduced DPC is due to menstrual phase-specific deficits in proprioception.

Timing therapeutic donor inseminations in natural cycles: human chorionic gonadotrophin administration versus urinary LH monitoring

This cohort study assessed whether timing therapeutic donor sperm inseminations (TDI) in natural cycles (NC) using ultrasound monitoring and ovulation trigger with human chorionic gonadotrophin (US/HCG) improves cumulative live birth rates (LBR) compared with detection of LH surge with urinary kits (u-LH). It included 232 normo-ovulatory women aged ≤40 years, undergoing 538 TDI in NC between 2011 and 2014. In the u-LH group (113 women, 267 cycles), TDI was performed the day following a positive test. In the US/HCG group (119 women, 271 cycles), ovulation was triggered with HCG when a follicle ≥17 mm was noted, and TDI performed 36 h later. The first three cycles were analysed per patient. Groups were comparable for baseline characteristics. Cumulative LBR were comparable between u-LH and US/HCG groups (31.47% versus 23.11%, respectively) (log-rank test). A generalized estimating equation analysis was performed to compare outcomes per cycle. The LBR per started cycle was comparable between the u-LH and US/HCG groups (12.4% versus 9.2%, respectively). Cancellation rate was significantly higher with u-LH (19.1% versus 11.4%, P = 0.011), but did not impact overall outcomes. In conclusion, urinary LH monitoring is as effective as ultrasound monitoring and ovulation trigger with HCG in TDI performed in NC.

COMPARISON BETWEEN TWO FET CYCLE METHODS WITH AND WITHOUT URINARY LH SURGE MEASUREMENT WITH URINARY LH KIT

The objective of this study is to assess the effectiveness of adding urinary LH surg e kit to hormonal prepared frozen embryo transfer (FET) cycles. In this prospective clinical trial, 48 patients enrolled in two groups. Endometrial hormone priming in both groups was similar; but i n group A, from day 10 of cycle, urinary LH surge detection was started embryo transfer (ET) scheduled after first positive test. In group B, ET was done after reaching endometrium thic kness to at least 7 mm. The duration of cycle, the frequency of ultrasound monitoring, the total dosage of estrogen consumption an d the result of cycle were measured. The duration of cycle before ET in group A was shorter (8.79 ± 1.14 VS 11 ± 1.47 days, P Value: 0.0005), the number of ultrasound repetition also was lesser (2.42 ± 0.58 VS 3.67 ± 0.86, P Value: 0.001). Respectively, in group A the total dosage estrogen consumption was less than group B (35.58 ± 5.2 VS 46.83 ± 5.27 mg, P value: 0.0005). The pregnancy rate in group A was more than group B, although it was not significantly different ( 37.5 % VS 25 % , P value: 0.52). It see ms except endometrial characters, assurance about the best time for embryo implantation prevent wasting valuable frozen embry o by incorrect timing of thawing and transfer.

150 USING A LUTEINIZING HORMONE SURGE DETECTION TEST, PREDI&amp;apos;BOV&amp;reg;, TO OPTIMIZE THE TIME OF ARTIFICIAL INSEMINATION DURING A SUPEROVULATION PROTOCOL IN A HOLSTEIN HEIFERS HERD

Insemination of superovulated bovine donors in due time is of central importance for fertilization and embryo viability. A preliminary test focusing on LH surge detection during superovulation (unpublished datas) indicated that one quarter of the donors present LH surges 12 to 24 h before heat observation (which could correspond, in the case of AI after heat observation, to post ovulation AI). Therefore, it was hypothesised that the average number of embryos per flush could be improved by inseminating donors with early LH surge 12 h after the beginning of the LH peak whenever the heat occurs.In a donor herd station, a trial was performed with 54 Holstein heifers, equipped with Heatime® tags (system detecting the peak activity linked to the heat) collected twice or 3 times after the following superovulation protocol: D-6 to D-11 = reference heat; D0 = input of an implant of norgestomet (Crestar®); D2 8:00 = first FSH (Stimufol®) injection (FSH1); D4 8:00 = cloprostenol (Estrumate®) injection; D4 16:00 = implant removal; D5 8:00 = FSH7 and first LH surge detection test (Predi'Bov®); D5 16:00 = FSH8 and 2nd Predi'Bov® test. Two AI's at interval of 8 to 16h were done (AI's were performed either at 9:00, or between 17:00 and 19:00). For the standard protocol (= STA), thefirst AI occurred after heat observation or activity peak detection by Heatime (whatever the Predi'Bov® test results were). For the adjusted protocol (= ADJ), the first AI occurred from 11 to 16 h after the first positive Predi'Bov® test result or like STA protocol if both results were negative. Heifers followed alternately the 2 protocols, 27 beginning with the ADJ protocol, 27 others with the STA one. LH surge precocity was not repeatable among donors. In the case of an early LH surge detection (one positive Predi'Bov® test), the heat activity peak occurred from 2 to 8 h after the FSH8 for 44% of the flushes, from 8 to 24 h after FSH8 for 54% of the flushes and never for 2% of the flushes. When no early LH surge was observed, the heat activity peak occurred more than 8 h after FSH8 for 78% of the flushes. Interval of heat activity peak-FSH8, IA1-heat activity peak and IA1-early LH surge were highly variable but did not effect the mean number of viable embryos. However, we observed a significant effect (P = 0.04) of the precocity of the heat on the average number of total embryos: 13.8 ± 8.4 v. 11.1 ± 8.1 when the interval heat activity peak-FSH8 had been respectively &lt;8 h or ≥8 h, respecively. Among the 148 collections, 74 were done after the STA protocol, 74 after the ADJ protocol and 70 followed an early LH surge. The adjustment of the AI depending on the detection of an early LH surge (ADJ protocol) had a significant positive (P = 0.04) effect on the mean percentage of viable embryos per flush (52% ± 28 in STA group and 62% ± 31 in ADJ group). Nevertheless, regarding the mean number of viable embryos, this effect failed to reach significance (P = 0.23) (respectively 5.7 ± 5.1 in STA group and 6.7 ± 6.7 in ADJ group). A larger study on more animals is necessary to obtain a significant difference in the number of viable embryos.

Human chorionic gonadotropin administration vs. luteinizing monitoring for intrauterine insemination timing, after administration of clomiphene citrate: a meta-analysis

To systematically compare hCG administration as a method for intrauterine insemination (IUI) timing with conservative urinary LH surge detection in infertility treatment. Meta-analysis of prospective and retrospective trials. Tertiary fertility and IVF center. One thousand four hundred sixty-one patients who received hCG after a clomiphene citrate regimen, compared with 1,162 patients who had an LH surge detection for IUI timing. Both MEDLINE and Cochrane Collaboration were searched. References of retrieved articles were included in the search. The meta-analysis included all controlled trials examining the effectiveness of hCG administration before IUI on clinical-pregnancy rates in comparison with LH detection. Two independent reviewers performed data extraction. Pregnancy rates. Seven studies with 2,623 patients were included in the meta-analysis (1,461 patients received hCG, and 1,162 had LH surge detection). When all studies were combined, patients who received hCG before IUI demonstrated lower clinical-pregnancy rates than did women who had IUI after spontaneous ovulation (odds ratio, 0.74; 95% confidence interval, 0.57-0.961). In subgroup analysis of studies that considered ovulatory dysfunction to be the infertility reason, the results favored women who received hCG. In contrast, across studies that reported male factor as the infertility reason, as well as across studies including women with unexplained infertility, results appeared to favor the LH surge detection approach. However, none of those subgroup analyses reached statistical significance. Available data do not demonstrate a consistent, clinically important benefit of hCG-induced ovulation compared with spontaneous ovulation for IUI timing.

Transrectal ultrasonic diagnosis of ovarian follicular cysts in goats and treatment with GnRH

Cystic ovarian disease is an important cause of reproductive failure. The objective of this study was to evaluate transrectal ultrasonography as a diagnostic tool and gonadotropin-releasing hormone (GnRH) as a therapeutic approach for ovarian follicular cysts in goats. Goats were considered to have a follicular cyst(s) if a non-echoic structure >10 mm in diameter was detected in the absence of corpora lutea (CL) in three ultrasonic examinations performed at 5-day intervals. After diagnosis (Day 0), goats with ovarian follicular cysts ( n=5) were treated with a single bolus injection of 10.5 μg synthetic GnRH followed by administration of 125 μg prostaglandin F2α (PGF2α) 10 days later. Five blood samples were collected at 5-day intervals for determination of progesterone and estradiol-17β. For detection of LH surge, blood samples were collected every 2 h. Ovulation rate was determined and pregnancy was confirmed by transrectal ultrasonography. The results showed that transrectal ultrasonography is reliable for diagnosis of ovarian follicular cysts and the mean diameter of the follicular cysts was 12.6±0.4 mm. Plasma concentrations of progesterone and estradiol-17β at the time of diagnosis of follicular cysts (Day 0) were 0.7±0.2 ng/ml and 12.7±0.9 pg/ml, respectively. The concentration of progesterone increased to 4.0±0.5 ng/ml 10 days after administration of GnRH indicating luteinization of the ovarian follicular cysts concomitant with a decrease in the concentration of estradiol-17β (3.5±0.4 pg/ml). Administration of GnRH to cystic goats resulted in a surge of LH within 2 h of treatment. The interval from PGF2α injection to the preovulatory LH surge was 62.8±1.4 h. All goats exhibited estrus 55.2±2.3 h after PGF2α injection and four goats out of the five ovulated. The ovulation rate was 1.5±0.3. In conclusion, results of this study suggest that transrectal ultrasonography is a reliable tool for diagnosis of ovarian follicular cysts. In addition, GnRH can be used to effectively treat ovarian follicular cysts in goats with 80% success rate.

Comparison of several one-step home urinary luteinizing hormone detection test kits to OvuQuick®

Objective: To compare clinical accuracy and ease of use for several of the new rapid one-step home urinary LH detection kits compared with the preexisting OvuQuick brand LH detection kit (designated as the standard).Design: Prospective cohort study.Setting: University-based infertility clinic.Patient(s): All women undergoing intrauterine inseminations at the clinic, regardless of infertility diagnosis, were offered enrollment during a 28-month study period.Intervention(s): Each participant was supplied three one-step test kits (OvuQuick One-Step, ClearPlan Easy, and SureStep) in addition to a multistep OvuQuick test kit and instructed to run the tests in parallel on the same urine sample and to record the results. Urine testing was performed every 12 hours, beginning 3 days before the anticipated onset of an LH surge, and continued with the one-step kits every 12 hours for 48 hours after the surge was first detected by OvuQuick. Subjects also completed questionnaires evaluating the use of each test kit.Main Outcome Measure(s): Correlation of LH surge detection by one-step kits in comparison to surge detection by OvuQuick. Satisfaction and ease of use questionnaires.Result(s): Sixty-three volunteers returned useable data, from which 81 evaluable cycles were analyzed. The majority of patients found the newer one-step kits to be easier to use and less time consuming than OvuQuick. The three one-step kits detected the LH surge within ± one testing period (±12 hours) of detection by OvuQuick 68%–84% of the time. OvuQuick One-Step, with modified instructions allowing for an equal color intensity in the test and reference areas, had the highest correlation with OvuQuick (84%). However, with a study power (α = 0.05, β = 0.10) sufficient to detect a 10% difference between Ovuquick and each one-step kit, all one-step kits were statistically equivalent to each other. There was no cycle in which a one-step kit detected a positive LH surge but OvuQuick did not.Conclusion(s): One-step urinary LH kits are easier for patients to use than a multistep home urinary LH kit and have reasonable correlation with the multistep kit when used clinically for timing artificial inseminations.

Reliability of Ovulation Tests in Infertile Women

In Brief Objective To assess the reliability of the most widely used clinical methods for predicting or confirming ovulation. Methods We monitored spontaneous cycles in 101 infertile women using basal body temperature (BBT), transvaginal ultrasound, a urinary stick system for LH surge, and three serum progesterone measurements in the midluteal phase. Transvaginal ultrasound monitoring was standard for ovulation detection and sensitivity. We calculated specificity and accuracy of each method compared with that standard. Results Follicular development and ultrasound evidence of ovulation were confirmed in 97 of 101 cycles (96%). Urinary LH surge preceded follicular rupture assessed by ultrasonography in all cycles and showed concordance with ultrasound-evidenced ovulation in 98 of 101 cases. The timing of BBT nadir had wide variability, and BBT and ultrasonography agreed in a similar percentage of cases (74%). Midluteal serum progesterone assessments showed ovulatory values in 93 subjects, and ovulation was concordant with ultrasonography in 90 subjects. Conclusion Urinary LH was accurate in predicting ovulation with ultrasonography as the standard for detection, but time varied widely. The nadir of BBT predicted ovulation poorly. The BBT chart was less accurate for confirming ovulation, whereas a single serum progesterone assessment in midluteal phase seemed as effective as repeated serum progesterone measures. Ultrasonography, urinary LH surge detection, and serum progesterone assessment seem to be the most effective methods for predicting and confirming ovulation.

Therapeutic cup insemination with cryopreserved donor sperm: prognostic value of cervical mucus score at insemination and the number of motile sperm in mucus at 24 hours

To examine the prognostic value of cervical mucus score at insemination and the number of motile sperm in mucus 24 hours after therapeutic cup insemination with cryopreserved donor sperm. Retrospective analysis. Academic tertiary medical center. One hundred thirty-eight women with confirmed bilateral tubal patency who received therapeutic cup inseminations with cryopreserved donor sperm between 1986 and 1993. All insemination cycles were monitored with serial daily urinary LH determinations with a single (n = 312) insemination or two inseminations (n = 212) performed on and/or 1 day after the day of LH surge detection. A single examiner assigned cervical mucus scores in all insemination cycles and recorded the number of motile sperm in mucus 24 hours after the first insemination in dual insemination cycles. Pregnancy rate during various cervical mucus and motile sperm scores. Ninety-one women conceived (66%) and seven of these achieved two pregnancies. The overall pregnancy rate per insemination cycle was 18.7%. Age and day of insemination were the only variables identified as having significant influence on cycle outcome. Pregnancy occurred with decreasing frequency as patient age increased and was nearly twice as likely after insemination on the day after the urinary LH surge as on the day of surge detection. Insemination the day after the urinary LH surge is superior to the day of surge detection. Cervical mucus score and the number of motile sperm in mucus 24 hours after therapeutic cup insemination with cryopreserved donor sperm do not correlate with cycle outcome.

High doses of oral contraceptives do not alter endometrial α1 and αvβ3 integrins in the late implantation window

To assess the effects of an emergency contraceptive agent on the distribution of integrin heterodimers during that part of the implantation window. Prospective, case-controlled study in a university-based Population Program. In the first ovulatory control cycle after the detection of LH surge, patients had endometrial sampling 11 days after the surge. In the next cycle the procedure was repeated 2 days after the administration of a postcoital contraceptive agent on day 9 after LH surge (100 g ethinyl E2 and 2 mg norgestrel). The effects of postcoital contraceptives on the expression of integrin heterodimers (alpha 1 and alpha v beta 3 subunits) reported to be unique to secretory phase was determined. All six specimens were consistent histologically with days 24 and 25 of the menstrual cycle by light microscopy. Using immunohistochemistry, strong membrane staining of endometrial glandular cells and superficial epithelium for both alpha 1 subunit and vitronectin (alpha v beta 3) receptor was observed in treatment and controls. No diminution of intensity or distribution was observed relative to pretreatment controls. There is no apparent change in the level of these two integrins in the human endometrium when high-dose oral contraceptives are given in the later stages of the implantation window. This suggests that the high doses of steroids used in emergency contraceptives may exert their effect through more complex mechanisms than endometrial cell surface changes.