Gonadotropin Injection Research Articles

Pregnancy outcomes in infertile patients undergoing intracytoplasmic sperm injection and two interval programs of hCG-to-oocyte aspiration

This study aimed to determine the outcomes of intracytoplasmic sperm injection (ICSI) if oocyte retrieval was done 32-34 hours or 34:05-36 hours after human chorionic gonadotropin (hCG) injection. A randomized sample involving 186 patients with tubal failure was divided into groups A (96 patients) and B (90 patients). Intracytoplasmic sperm injection was performed on all patients according to described protocols. The number of oocytes retrieved, oocyte cumulus complex quality, number of fertilized eggs, and pregnancy rates were compared between groups. The total of oocytes retrieved in group B was significantly higher than in group A but not significant (P=0.068). The oocyte maturation rate was also significantly higher in the long interval group B than in the short interval group A (P=0.039). There was a significant difference between the two groups in terms of fertilization rate (0.040), and the pregnancy rate in group B was higher than that in group A, but it was not significant (P=0.055). The prolonged interval could also increase the pregnancy rate, but it was not significant. It seems that if the interval between hCG priming and oocyte retrieval is prolonged, the percentage of the number of oocytes retrieved, mature oocytes (MII), and fertilized oocytes increases.

Nomogram models to predict low fertilisation rate and total fertilisation failure in patients undergoing conventional IVF cycles

ObjectivesTo establish visualised prediction models of low fertilisation rate (LFR) and total fertilisation failure (TFF) for patients in conventional in vitro fertilisation (IVF) cycles.DesignA retrospective cohort study.SettingData from August 2017...

Is There any Role for Granulocyte Colony Stimulating Factor in Improvement of Implantation in Intrauterine Insemination? A Prospective Double-Blind Randomized Control Trial.

Granulocyte colony stimulating factor (GCSF) has been introduced as an immunomodulatory agent by increasing implantation rate in vitro fertilization (IVF) patients but it has not been studied in intrauterine insemination (IUI) patients. The aim of this study is to answer the role of GCSF in implantation rate of IUI. In this prospective double-blind randomized control trial, 320 eligible patients were enrolled, who were referred to the referral infertility clinic of Shiraz University of Medical Sciences from February 2018 till the end of 2019. They were divided into two groups randomly. After collecting the demographic data, all patients received clomiphene citrate from the 5th day of the menstruation cycle for 5 days. 50-150 units of recombinant purified follicle-stimulating factor (FSH) were started from the 8th day of the cycle. Follicle monitoring was done by transvaginal sonography till a mature follicle of 18 mm or more was developed. Human chorionic gonadotropin (HCG) injection was done in both groups with intrauterine administration of 300 μg GCSF in the case group and normal saline in the control group simultaneously. After 36 hours, IUI was performed. The clinical pregnancy, miscarriage, and ongoing pregnancy rates of both groups were calculated by SPSS software. The results showed improvement of clinical pregnancy rate [15.38% vs. 13.81% OR=1.17 (0.62-2.21)], miscarriage rate [3.84% vs. 5.26% OR=0.74 (0.25-2.20)] and ongoing pregnancy rate [11.53% vs. 8.55% OR=1.37 (0.65-2.92)] in the GCSF group compared to the control. However, the results revealed no statistically significance (P>0.05). Although it was not statistically significant, 300 μg Intrauterine GCSF administration simultaneously with hCG injection in standard IUI procedure might increase the pregnancy outcomes. Further studies are warranted (registration number: IRCT201212079281N2).

Influence of the sodium fluoride on the development and survival of the loach embryos

Background: The study of fluoride effects at the cellular level is still essential for biophysics, medicine, and ecology as one of the most common environmental pollutants. Its impact on embryonic objects is poorly understood. Objectives: The aim of the work was: 1) to study the effect of sodium fluoride (in the minimum concentration to inhibit growth) on the morphological development of loaсh embryos; 2) evaluation of the degree of survival of embryos in the presence of sodium fluoride in the incubation medium and determination of the coefficient Ks. Materials and methods: Ovulation in loach females (Misgurnus fossilis L.) was stimulated by intramuscular injection of female chorionic gonadotropin (500 units), eggs were obtained by 36 h after stimulation, fertilized in Petri dishes with a suspension of sperm according to Neifach A. A. The stages of development were observed visually used a binocular microscope MBS-9 with a photo camera. The experimental embryos were incubated in Goltfreter's solution with the addition of sodium fluoride to a final minimum concentration to inhibit growth of 500 μmol/l. Results: Sodium fluoride inhibits the development of loach embryos and leads to developmental defects. The noticeable developmental defects caused by sodium fluoride were a reduction in the size of the larvae's head and tail, low body pigmentation, changes in the eye diameter, and embryonic touch reflex. As a result of the accumulation of fluoride in embryonic cells, on the third day of development, embryonic mortality increased to 88,9%. On 12 days under the action of sodium fluoride, the total number of larvae was about 2%. Conclusions: The ability of NaF to act as a direct teratogen was tested on the cold-blooded embryo model, the same effect was found by other investigators on the FETAX model. The possibility that sodium fluoride may cause toxic and/or neuromuscular developmental defects in human embryos also should be considered. Avoiding excessive getting of fluoride in the body by limiting the consumption of foods or beverages high in fluoride, the use of fluoride in dental care products, etc. requires detailed assessment.

Learning from Online Video Education (LOVE) improves confidence in fertility treatments: a randomized controlled trial

Fertility treatments like in vitro fertilization (IVF) or oocyte cryopreservation (OC) require the daily use of injectable gonadotropins and has been associated with treatment burden and attrition from fertility treatment. We conducted a randomized clinical trial to determine (1) whether educational videos about fertility medications improved infertility self-efficacy scale (ISES), fertility quality of life treatment (FertiQoL-T), and Perceived stress scale (PSS) scores and (2) if such videos improved confidence and reduced medication errors during a first ovarian stimulation cycle. Participants were given access to an online portal with randomized access to either placebo control videos focused on an orientation to IVF or experimental videos that reviewed the preparation and administration of medications used during ovarian stimulation in addition to the placebo videos. Participants completed pre and post-treatment questionnaires. 368 patients enrolled and 257 participants completed the study. There were no differences in ISES, FertiQoL-T or PSS scores between the two groups in an intention-to-treat (p = 0.18, 0.72, and 0.92, respectively) or per-protocol analysis (p = 0.11, 0.38, and 0.37, respectively). In the per protocol analysis, participants who watched experimental videos were four-fold more likely to report confidence administering medications OR 4.70 (95% CI: 2.10, 11.1; p < 0.01) and were 63% less likely to make medication errors OR 0.37 (95% CI: 0.14, 0.90; p = 0.03). Participants had similar likelihoods of rating videos as helpful and recommending videos to others (p = 0.06 and 0.3, respectively). Educational videos about fertility medications may not influence psychological well-being but might improve confidence in medication administration and reduce medication errors. Trial registration number: NCT02979990.

The use of stimulation tests for the differential diagnosis of delayed puberty in boys. How to increase the specificity of the method?

BACKGROUND: In patients with a constitutional delay of puberty starts and ends completely without any medical intervention. In adolescents with hypogonadotropic hypogonadism puberty is absent or does not continue its development. Differential diagnosis of the conditions is complicated due to lack of standard recommendations for the selection, conducting and assessment of stimulation tests.&#x0D; AIM: To assess the information content and find ways to increase the specificity of stimulation tests with triptorelin and corionic gonadotropin in relation to hypogonadotropic hypogonadism.&#x0D; MATERIALS AND METHODS: We examined 44 adolescent boys aged 13.517 years with delayed puberty. Sexual development was assessed according to Tanner scale, bone age (X-ray of the non-dominant hand according to the Greulich atlas). All boys were tested with triptorelin. The test with one- and three-day intramuscular injection of human chorionic gonadotropin was performed in 26 and 35 patients, respectively. Statistical analysis was performed using the StatTech v. 2.6.1 (developer Stattech LLC, Russia). To assess the diagnostic significance of quantitative signs in predicting a certain outcome the ROC-curve analysis was performed.&#x0D; RESULTS: It was revealed that a negative test with triptorelin was observed in some patients with constitutional delay of puberty. Threshold stimulated luteinizing hormone and follicle stimulating hormone levels were set (8.90 and 5.90 IU/l respectively). Gonadotropins values equal to or lower than selected thresholds allow diagnosing of hypogonadotropic hypogonadism with high sensitivity and specificity. Threshold testosterone levels stimulated by one- and three-day administration of human chorionic gonadotropin were determined (2.11 and 5.84 nmol/l respectively). Testosterone values equal to or lower than selected thresholds allow diagnosing of hypogonadotropic hypogonadism with high sensitivity and specificity. A high degree of positive correlation was found between stimulated luteinizing hormone levels and stimulated testosterone levels during a three-day test with human chorionic gonadotropin.&#x0D; CONCLUSIONS: A negative test with triptorelin is observed in some patients with constitutional delay of puberty. The specificity of the test can be improved by using threshold stimulated levels of luteinizing hormone and follicle stimulating hormone (8.90 and 5.90 IU/L, respectively). The use of the threshold levels of testosterone (2.11 and 5.84 nmol/l within the one- and three-day functional tests of the testicles respectively) can help to increase the specificity of the considered outdated stimulation tests with human chorionic gonadotropin.

Trial design and protocol of randomized controlled trial comparing the efficacy of combined letrozole and clomiphene versus only letrozole as a method of ovulation induction in women with polycystic ovarian syndrome (CCLOP trial)

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Both clomiphene (CC) and letrozole are commonly used oral ovulation induction agents, with different mechanism of action. Apart from letrozole or CC, options for ovulation induction in polycystic ovarian syndrome (PCOS) patients are limited and thus leaving the use of gonadotropin injections as the only option of ovulation induction in these patients. The objective of this study is to evaluate the efficacy of combined therapy of letrozole and CC compared to the use of letrozole alone to achieve ovulation in infertile women with PCOS.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This will be a single-centre, double arm, triple-blind randomized controlled trial. The study was conducted after taking approval from institutional ethics committee and was prospectively registered with the clinical trials registry- India. Women were randomly assigned to receive a combination of 2.5 mg letrozole and placebo daily or a combination of 2.5 mg letrozole and 50 mg CC daily on cycle days 3–7 for one treatment cycle.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;If combination of clomiphene and letrozole is proved to be more efficacious than letrozole alone, there will be several breaks through advantages in the management of infertility. The novel method of ovulation induction with combined letrozole and clomiphene will bring down overall cost of infertility treatment.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Trial registration:&lt;/strong&gt; The study is prospectively registered with the clinical trials registry- India CTRI/2020/09/028012.&lt;/p&gt;

The effect of controlled ovarian hyperstimulation on ovarian reserve via PTEN pathway.

Graphical abstract This study was carried out to investigate whether repeated controlled ovarian hyperstimulation (COH) affects ovarian reserve. For this reason, we aimed to show possible changes in the expression of PTEN and FOXO3, which are involved in preserving the over-reserve, after applying the COH protocol methods. For this purpose, 18 young Wistar albino female rats (8 weeks old) were randomly assigned as group 1 (control), group 2, and group 3 as 6 subjects in each group. Experimental groups were treated with 10 IU/0.1 mL pregnant mare’s serum gonadotropin and a COH protocol consisting of 10 IU/0.1 mL human chorionic gonadotropin injection after 48 h. This procedure was applied three and five times to group 2 and group 3, respectively. For the control groups, the same procedures were performed with 0.1 mL of 0.9% sodium chloride solution. At the end of the experiment, the ovarium tissues were placed in a 10% neutral formaldehyde solution for light microscopic examinations. In histological sections stained with hematoxylin and eosin, the number of ovarian follicles was determined using the physical dissector method. However, the expression of PTEN, FOXO3, and LH-R molecules was evaluated by immunohistochemical methods. As a result of our study, it was concluded that COH administration reduces the expression levels of PTEN and FOXO3 proteins and LH-R, which are among the essential components of the PIK3 intracellular signaling pathway and also increased the levels of hormones such as follicle-stimulating hormone, estradiol, and luteinizing hormone, which are over-reserve markers, and causes adverse effects on the histological structure, oocyte morphology, and number of ovaries.Lay summaryToday, approximately 10–15% of couples experience fertility problems. However, assisted reproductive techniques help people with fertility problems to get pregnant. The main purpose of these techniques is to put the sperm and egg together outside the woman’s body where the eggs are fertilized and then to return the fertilized eggs (embryos) to the womb. During a woman’s menstrual cycle, several hormones influence the growth of the eggs. This process can be mimicked by using various medications. Medication is given to increase the number of eggs that develop. However, this method is not the same as normal ovulation. Therefore, in our study, we wanted to examine the effect that developing multiple follicles has on the number and quality of eggs remaining for the future.

P-426 Placental pathology following Intrauterine Insemination (IUI) with or without Ovarian Stimulation (OS)

Abstract Study question Do placental weight percentiles (PW %iles) and abnormality rates (PAR) differ in singleton-livebirths following IUI with or without OS [oral medications (OM), and injectable gonadotropins]? Summary answer Following singleton-livebirths, PW did not differ between groups, albeit over half of placentas were ≤25th%ile. Placental anatomic abnormalities were more often seen in OM cycles. What is known already ART data suggest a possible association between stimulation-induced supraphysiologic estradiol levels and increased risk of placental abnormalities, as well as subsequent placental-mediated pregnancy complications, such as preeclampsia. Whether there is an association between OS protocols for IUI and placental pathology remains unknown. Study design, size, duration Data from 975 IUI(±OS) cycles resulting in singleton livebirths at a large academic fertility center between 01/2004 and 01/2021, were retrospectively reviewed. In 386 cycles a full placental pathologic examination was available. Placentas were stratified by OS regimen into three groups: gonadotropins (n = 222), OM [Clomiphene Citrate (CC)/Letrozole (LTZ); n = 129], and unstimulated / natural (n = 35). PW and PAR were compared between groups. Participants/materials, setting, methods Participants: Women delivering a singleton liveborn following IUI(±OS) treatments with placental pathology available. Outcome Measures: PW (grs &amp; %iles), and PAR (classified as anatomic, inflammatory, infectious, and vascular/thrombotic). Statistics: Regression analysis was utilized to compare PW and PAR between groups, adjusting for potential confounders (PW: maternal and gestational age, BMI, infertility diagnosis, medical complications, infant gender; PAR: maternal and gestational age, BMI, race). Adjusted Odds Ratios (adjOR, 95%CI) were calculated for the latter. Main results and the role of chance Mean(±STDEV) PW (grs) were 451.7(±113.3), 449.2(±102.4), and 481.8(±99.8), for the gonadotropins, OM, and natural groups, respectively. Interestingly, over half of the placentas in all three groups were ≤25th %ile (58.6%, 56.1%, and 52.9%, for gonadotropins, OM, and natural, respectively, p=.249), while 41.8%, 46.4%, and 38.2% were below the 10th %ile (for gonadotropins, OM, and natural, respectively, p=.598). Adjusted PW differences, and adjOR for small placenta (≤10th %ile) did not differ between groups [PW OR(95%CI): 5.6(-17.9-29.2), -28.1(-71.4-15.2), -11.7(-52.6-29.3); small placenta OR(95%CI): 1.04(0.62-1.76); 1.27(0.40-4.01), and 0.96(0.34-2.74) for OM vs. gonadotropins, OM vs. natural, and gonadotropins vs. natural, latter as ref. ]. Regarding PAR, anatomic(43.7%, 52.7%, and 40%, p=.192), inflammatory(20.7%, 27.1%, and 20%, p=.354), infectious(32.9%, 33.3%, and 31.4%, p=.978), and vascular/thrombotic(42.3%, 41.9%, and 42.9%, p=.993) abnormalities rates did not differ between gonadotropins, OM, and natural, respectively. AdjORs(95%CI) for inflammatory, infectious, and vascular/thrombotic abnormalities did not differ significantly between groups. However, anatomic abnormalities were more frequent among OM compared to gonadotropin and natural cycles [adjOR(95%CI): 1.76(1.06-2.91), p=.028, gonadotropins as ref.; 2.52(1.05-6.05), p=.038, natural as ref.]. Limitations, reasons for caution This study is limited by its retrospective nature. Unfortunately, placental pathology was available only in conceptions clearly identified as resulting from IUI(±OS) treatments. However, birth weights did not differ between those with and without available placental pathology. Natural/IUI cycles were limited in numbers not allowing meaningful conclusions. Wider implications of the findings Between IUI-conceived, singleton-livebirths with available placental pathology, mean PW did not differ significantly. However, a higher-than-expected percent of placentas were below the expected %iles, suggesting that IUI(±OS) might be associated with altered placental growth. Placental anatomic abnormalities were more common among OM cycles, compared to gonadotropins, and n atural IUI cycles. Trial registration number Not applicable

O-184 The impact of cryopreserved sperm on Intrauterine Insemination (IUI) outcomes: Is frozen as good as fresh?

Abstract Study question Are the outcomes of IUI cycles [with or without ovarian stimulation (OS)] comparable when frozen instead of fresh-ejaculated sperm is utilized? Summary answer Overall, clinical outcomes did not differ significantly between frozen and fresh sperm IUI cycles, although specific subgroups might benefit from fresh sperm utilization. What is known already At present, data from animal studies point towards less favorable outcomes with frozen sperm utilization, implicating cryopreservation-induced damages to the cytoskeleton, DNA, and acrosome leading to adverse effects on spermatozoa’s motility, viability, and ability to fuse with the oocyte. Assisted Reproductive Technology (ART) data, mostly focusing on severe male factor infertility diagnoses, suggest no major differences between in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles utilizing frozen over fresh sperm, often surgically extracted. Nevertheless, contemporary data from IUI(±OS) cycles are still scarce. Study design, size, duration Data from 5335 IUI(±OS) cycles (time-period: 01/2004-12/2021) from a large academic fertility center were retrospectively reviewed. Cycles were stratified in two groups based on utilization of frozen instead of fresh-ejaculated sperm for the IUI [FROZEN (n = 1871, all infertility diagnoses), and FRESH (n = 3464, idiopathic infertility diagnosis only), respectively]. Cycle outcomes were compared between groups. Participants/materials, setting, methods Participants: women seeking IUI (±OS) treatments. Outcome Measures: HCG-positivity, clinical pregnancy (CP), spontaneous abortion (SAB) rates. Initial analysis included all cycles irrespective of OS regimen. Cycles were then stratified by OS regimen into three subgroups [injectable gonadotropins, oral medications (OM): clomiphene-citrate and letrozole, and unstimulated/natural]. Odds ratios (OR) for all relevant outcomes were calculated utilizing logistic regression and adjusted for maternal age, day-3 FSH, and OS regimen. Time-to-pregnancy and first-cycle only analyses were also performed. Main results and the role of chance Unadjusted HCG-positivity, and CP were lower in the FROZEN compared to the FRESH group (12.2% vs. 15.6%, p &amp;lt; 0.001; 9.4% vs. 13.0%, p&amp;lt;.001, respectively), which persisted only among OM after stratification (9.9% vs. 14.2% HCG-positivity, p=.030; 8.1% vs. 11.8% CPR, p=.041, for FROZEN compared to FRESH, respectively). Among all cycles, adjOR(95%CI) for HCG-positivity and CP were respectively: 0.75(0.56-1.02), and 0.77(0.57-1.03), ref: FRESH). Following stratification by OS regimen, adjOR(95%CI) for HCG-positivity and CP showed no difference between groups among gonadotropin and natural cycles but favored the FRESH group in OM cycles [HCG-positivity: 0.55(0.30-0.99); CP: 0.49(0.25-0.95), ref.: FRESH]. SAB odds did not differ between groups among OM and natural cycles but were lower in the FROZEN compared to FRESH group among gonadotropin cycles [adjOR(95%CI): 0.13(0.02-0.98), ref.: FRESH]. However, regarding the latter comparison, numbers were small and the 95%CI wide. When analysis was limited to first-cycles only and further stratified by OS regimen, the previously noted differences in CP and SAB odds no longer existed within the OS subgroups. Nevetheless, time-to-conception was slightly longer in the FROZEN compared to the FRESH group (3.84 vs. 2.58 cycles, p&amp;lt;.001). Limitations, reasons for caution Study is limited by its retrospective nature. The two groups differed somewhat in age, infertility diagnosis, utilized OS regimen, and as expected in total motile sperm counts. Despite the less favorable characteristics of the FROZEN group, no detrimental effect of sperm cryopreservation on IUI outcomes was noted. Wider implications of the findings Our study, the largest to date, showed no significant difference in IUI outcomes between cycles utilizing frozen instead of fresh-ejaculated sperm. Although, specific subgroups might benefit from fresh sperm utilization and time-to-pregnancy might be shorter with fresh over frozen sperm, patients should be counselled about the non-inferiority of frozen sperm. Trial registration number Not applicable

Comparing Naltrexone and Metformin Pretreatment for Inducing Ovulation in Patients With Polycystic Ovary Syndrome in Intrauterine Insemination Cycles

Objectives: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women. Hyperinsulinemia and insulin resistance are normally observed in PCOS patients and metformin is used to treat this disease. The evidence indicates that the opioid system plays a role in the pathogenesis of the PCOS. Based on the above-mentioned explanation, the present study evaluated the role of opioid antagonist (naltrexone) in PCOS-induced infertility compared to metformin. Materials and Methods: Totally, 120 patients afflicted with PCOS were assigned to three groups based on Rotterdam diagnostic criteria, with a body mass index (BMI) of 25-30 kg/m2 . The first group received naltrexone (50 mg/d) for 8 weeks. In addition, the second group were injected with metformin 1000 and then 1500 mg/d for the first and seventh weeks, respectively. Finally, the third group entered the intrauterine insemination (IUI) without prior therapeutic treatment. Then, the groups were compared in terms of the amount of estradiol produced per day of human chorionic gonadotropin injection and the total amount of gonadotropin needed, the number and size of the adult follicles, the number of days of taking the drug, and incidence of pregnancy-induced abo Results: Based on the results, the mean of infertility duration was not significant among the three groups (P=0.782). Further, the mean fasting insulin level between the metformin and control groups represented a significant difference (P=0.045). The average number of days to trigger patients in the 3 groups was not significant (P=0.346). Although the average number of follicles between metformin and naltrexone groups was not significant, it was higher in the naltrexone group. Finally, the average BMI of the naltrexone group after the treatment was lower compared to before treatment (P≤ 0.001). Conclusions: In general, the number of receiving days and the dose of the drug in the naltrexone group was lower compared to the metformin group. Furthermore, the number of mature follicles in both ovaries and the serum estradiol level in the naltrexone group was higher compared to the metformin group.

The Success of Ovulation Induction with Letrozole and Gonadotropins in Obese and Nonobese Women: A Study from a Tertiary Center.

Background Letrozole, an aromatase inhibitor, is suggested as a first-line drug for ovulation induction in women with polycystic ovary syndrome (PCOS) especially in obese women. Letrozole has also been used in women with unexplained infertility with similar rates of success to clomiphene. However, literature on letrozole and gonadotropins in obese and nonobese women is sparse. Hence, this study was done to assess the success of ovulation induction (OI) with letrozole plus follicle stimulating hormone (FSH) in obese (BMI ≥ 30 kg/m2) and nonobese women (BMI < 30 kg/m2). Methods A retrospective descriptive cohort study was conducted involving 135 women who underwent OI with letrozole plus follicle stimulating hormone therapy and either timed intercourse or intrauterine insemination. The data was collected from the hospital information system, including the age, body mass index, the type of infertility, number of induction cycles with letrozole, number of gonadotropin injections, and the pregnancy occurrence following treatment. SPSS was used to analyze the data. Results There were 135 women who used FSH injections along with letrozole. Of this, 28.5% obese women got pregnant compared to 29.2% nonobese women, but this did not attain statistical significance (P = 0.75). About 70% of obese women and 57% on nonobese women had polycystic ovarian syndrome. The median number of FSH injections was six, and the interquartile range was 3 to 11. Conclusion Of the 135 women undergoing letrozole and FSH, there was almost an equal probability of pregnancy in the obese group (BMI ≥ 30 kg/m2) and nonobese women.

Hyperstimulation Syndrome of the Ovary: A review on clinical feature, pathophysiology, risk factors, and prevention.

Hyperstimulation syndrome of the ovary is a dangerous complication of ovulation induction during infertility treatment by gonadotropins stimulation and human chorionic gonadotropin injection. Increased capillary permeability, causing fluid leakage from the intravascular compartment, with the accumulation of fluid in the third-space and consequent intravascular dehydration, is the main change in the pathophysiology of Hyperstimulation syndrome of the ovary. Vascular endothelial growth factor (VEGF) is the main mediator in the development of Hyperstimulation syndrome of the ovary. The recent application of new modalities: GnRH antagonist protocol, GnRH agonist (GnRHa) triggering of ovulation and embryo/oocyte vitrification, facilitates the elimination of Hyperstimulation syndrome of the ovary associated with controlled control ovarian hyperstimulation(COH) for IVF program. In this manuscript, we reviewed the pathophysiology, clinical features, predisposing factors, and both primary and secondary arrangement for preventing Hyperstimulation syndrome of the ovary as there is no single measure to prevent OHSS totally. Therefore, categorizing the women based on their risk potentiality seems to be beneficial to direct the line of management as early as possible to avoid the emergence of Hyperstimulation syndrome of the ovary.

The Effect of Intrauterine Injection of Human Chorionic Gonadotrophin on Implantation Rate During ICSI Cycles: Systemic Review and Meta-Analysis

The Effect of Intrauterine Injection of Human Chorionic Gonadotrophin on Implantation Rate During ICSI Cycles: Systemic Review and Meta-Analysis

Influence of PMSG on Superstimulation and Embryo Development Following Somatic Cell Nuclear Transfer in Holstein Cows in the United Arab Emirates.

The present study investigated the effect of superstimulation to improve in vitro embryo production in the Gulf area, where the temperature is high. Holstein cows were classified into the control and superstimulation groups. Superstimulation was induced with a single intramuscular injection of pregnant mare serum gonadotropin (PMSG; 2500 IU) on day 14 of the estrus cycle (day 0; estrus). The development of follicles was evaluated by ultrasonography of the ovaries daily. At 40 h after the PMSG injection, oocytes were collected by the ovum pick-up (OPU) technique. OPU was performed at the same stage of the estrus cycle in the control group as in the superstimulation group. The number of follicles with a diameter of more than 6 mm and the number of retrieved cumulus-oocyte complexes were significantly higher in the superstimulation group than in the control group. Furthermore, the maturation rate was higher in the superstimulation group than in the control group. Cloned embryos were produced by somatic cell nuclear transfer using matured oocytes. The cleavage and blastocyst formation rates were significantly higher in the superstimulation group than in the control group. In conclusion, a single injection of PMSG can facilitate the efficient production of cloned cow embryos.

Effects of Acupuncture on Endometrium and Pregnancy Outcomes in Patients with Polycystic Ovarian Syndrome Undergoing in vitro Fertilization-Embryo Transfer: A Randomized Clinical Trial.

To observe the effect of acupuncture on endometrium and pregnancy outcomes in patients with polycystic ovary syndrome (PCOS) infertility undergoing in vitro fertilization-embryo transfer (IVF-ET). Eighty-three patients were randomly assigned to observation group (40 cases) and control group (43 cases) according to the random numbers generated by SPSS software. The patients of the two groups received GnRH agonist long protocol as a routine treatment. In the observation group, acupuncture was given at two acupoint groups for 30 min once every other day. Group 1 included Guanyuan (CV 4), Qihai (CV 6), Zhongji (CV 3), bilateral acupoints Zigong (EX-CA1). Group 2 included Mingmen (GV 4), Yaoyangguan (GV 3), bilateral Shenshu (BL 23) and Ciliao (BL 32). The two groups of acupoints were used alternately. The whole needling process was performed at the time of ovulation induction until the transplantation day and consisted of 3 courses, while the control group did not receive acupuncture interventions. The Gn dosage and Gn stimulation time, endometrial thickness and type (A, B, and C), serum oestradiol (E2) and progesterone (P) levels on the day of injection of human chorionic gonadotropin (hCG), clinical pregnancy rate, as well as live birth rate were observed. Adverse reactions were also be recorded. All patients were followed up for the pregnant rate 14 days after IVF-ET and live birth rate after pregnancy. All adverse reactions (AEs) of acupuncture were recorded during the trial. The Gn dosage and Gn stimulation time in the observation group were lower in the observation group than in the control group (P<0.01). The proportion of type A endometrium in the observation group were higher than that in the control group (P<0.05). The serum E2 and P levels on the day of hCG injection was lower and the clinical pregnancy rate was higher in the observation group compared to those in the control group (P<0.05). There was no serious AEs during this trial. Acupuncture can improve the proportion of type A endometrium, regulate the levels of serum E2 and P on the day of hCG injection, and improve the pregnancy rate in patients with PCOS infertility undergoing IVF-ET.

Cryptotanshinone Protects against PCOS-Induced Damage of Ovarian Tissue via Regulating Oxidative Stress, Mitochondrial Membrane Potential, Inflammation, and Apoptosis via Regulating Ferroptosis.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age. Cryptotanshinone (CRY) has been shown to be effective in reversing reproductive disorders, but whether it can be used in the treatment of polycystic ovary syndrome remains unclear. We aimed to explore whether the mechanism of cryptotanshinone (CRY) in the treatment of polycystic ovary syndrome (PCOS) can be driven via regulating ferroptosis. A rat model of PCOS was established by daily injection of human chorionic gonadotropin and insulin for 22 days. An in vitro model of ischemia-reperfusion (IR) of granulosa cells was established. The in vitro and rat models of PCOS were subjected to different treatments including ferroptosis activators and inhibitors, CRY, and MAPK inhibitor. Oxidative stress was evaluated by measuring the activities of SOD, MDA, and GSH-PX. Total body weight and ovarian weight, as well as the levels of LH and the LH to FSH ratio, significantly increased in rats with PCOS, compared with controls. The expression of Bax was increased in PCOS tissues while PGC1α, NFR1, GPX4, catalase p-ERK, and Bcl-2 were all downregulated. Ferroptosis activator, erastin, had effects similar to those of PCOS while the contrary was found with CRY and ferroptosis inhibitor treatment groups. In vitro, CRY inhibited oxidative stress, MMP, and NF-κB and activated MAPK/ERK signaling by regulating ferroptosis. Overall, this study indicated that CRY protects against PCOS-induced damage of the ovarian tissue, via regulating oxidative stress, MMP, inflammation, and apoptosis via regulating ferroptosis.

Reproductive efficiency of treated Karakul ewes with short-term progesterone and hCG injections during the non-breeding and breeding seasons

The aim of this study was to evaluate reproductive efficiency of ewes following a short-term treatment with progesterone (P4) plus human chorionic gonadotropin (hCG) injections. In Exp 1, ewes (n = 65) were used during the non-breeding season and received P4, three times every other day (n = 22, 3PHCG, IM) or a single dose of P4 (n = 21, PHCG). We injected hCG in all ewes 24 h after the P4 treatment, and distilled water in control group (n = 22). Blood collection were performed on days −13, −6 and + 8 relative to ram release. In Exp 2, during the breeding season, ewes (n = 66) were assigned to the 3PHCG (n = 33) and control (n = 33) groups described for Exp 1, and subsequently received PGF2α 48 h before ram release. Pregnancy diagnosis was performed on day 42 after the ram release which was done 24 h after the hCG injection. In Exp 1, Estrus, pregnancy rate at induced estrus, and lambing rates at the first cycle were greater in 3PHCG (81.8%, 59.1% and 54.5%) group compared with the PHCG (38.1%, 23.8% and 19%) and control (0%, 0% and 0%) groups (P < 0.05). In Exp 2, Estrus, pregnancy rate at induced estrus, and lambing rates at the first cycle were greater in 3PHCG (75.8%, 57.6% and 51.5%) group compared with the control (39.4%, 30.3% and 27.3%) groups (P < 0.05). To conclude, hCG injection 24 h after P4 administration is an effective protocol to induce fertile estrus during non-breeding season, and synchronize estrus and lambing of ewe in the breeding season.

Pregnancy rate in intrauterine insemination, is uterine biophysical profile of predictive value? A prospective study.

This study aimed at evaluating the value of uterine biophysical profile (UBP) scoring to predict the pregnancy rate after IUI. This prospective study was carried out on 85 women who were referred to our tertiary teaching center with infertility of male factor or unknown etiology infertility in 2018. To measure the uterine biophysical criteria, transvaginal ultrasonography (TVS) was performed on the day of beta-human chorionic gonadotropin (B-hCG) injection, and the results were evaluated based on positive B-hCG. 85 patients were included with a mean age of 30years; of those 12 (14.1%) were able to conceive. UBP (p = 0.151) and it's parameters (including endometrial thickness, number of endometrial layers, myometrial echogenicity, uterine artery pulsatility index, myometrial blood flow internal to arcuate vessels, endometrial blood flow in the third zone of endometrium, myometrial contraction frequency, and ovarian follicle (OF) size [p = 0.05, 0.89, 0.59, 0.79, 1, 1, 0.59, and 0.77, respectively]) were not significantly associated with pregnancy rate. 91.7% of the cases with positive pregnancy test results, had a UBP score of > 13; however, UBP score was not meaningfully associated with IUI treatment success rate (p = 0.15). UBP scoring system seems to need more data for external validation, or it might require modifications before implementation, as it may cause false reassurance.

Efficacy and safety of newly developed ganirelix acetate in infertile women for assisted reproductive technology: a prospective, randomised, controlled study

This study aimed to investigate the efficacy of Ganilever pre-filled syringe (PFS), a newly developed ganirelix acetate, for the inhibition of premature luteinising hormone (LH) surge in in vitro fertilisation (IVF). A prospective randomised controlled study was conducted (NCT03051087). A total of 236 women (Ganilever group: 114, Orgalutran group: 122) were finally analysed. The patients with LH of >10 mIU/mL on the day of human chorionic gonadotropin (hCG) injection were 0 (0.0%) and 3 (2.5%) in the Ganilever and Orgalutran groups, respectively (p= .25). The number of retrieved oocytes from two groups did not show any significant difference (12.0 ± 6.4 vs. 11.8 ± 6.3, p= .73). Furthermore, the two groups did not show significant differences in the number of good-quality oocytes and embryo, and the rate of fertilisation. Similar safety profiles were also observed. In conclusion, Ganilever PFS showed comparable IVF outcomes and safety profile in IVF, as compared to the Orgalutran. Impact Statement What is already known on this subject? Premature LH surge during controlled ovarian stimulation results in the induction of luteinisation of the immature follicles. Thus, gonadotrophin-releasing hormone (GnRH) antagonist protocol was suggested as an option for suppression of premature LH surge. Currently, one of GnRH antagonists being widely used is ganirelix acetate (Orgalutran®; Organon, Oss, The Netherlands). Ganilever pre-filled syringe (PFS) is a newly developed GnRH antagonist containing ganirelix acetate as an active ingredient. What do the results of this study add? Our study demonstrated that Ganilever PFS showed comparable IVF outcomes and patient safety profile in infertile women undergoing in IVF-ET, as compared to the Orgalutran. What are the implications of these findings for clinical practice and/or further research? The results of our study will provide another available GnRH antagonist to be used in patients with IVF.