gonadotropin-releasing hormone

The study was conducted to investigate the effect of dual trigger with gonadotropin-releasing hormone agonist (GnRH-a) and standard dose human chorionic gonadotropin (hCG) on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes in patients with a history of suboptimal ovarian response. In this randomized clinical trial, 52 infertile women who were referred to Royan Institute from November 2019 to November 2022 for a second treatment with IVF/ICSI cycles, and had a suboptimal ovarian response [the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) classification group I] in their previous cycle were evaluated. Ovulation stimulation was performed in all patients with the standard antagonist protocol. At the point of the final ovarian stimulation, patients were randomly assigned into two groups using the permuted block randomization method. In the dual trigger group, 0.2 mg of GnRH-a and two ampoules of recombinant hCG subcutaneously were administered to the patients at the same time. In control group, only two ampoules of recombinant hCG were injected subcutaneously. The ovarian stimulation outcomes and pregnancy rates were compared between groups utilizing appropriate statistical methods. The two groups were homogeneous in terms of baseline characteristics. The statistical differences were found between groups in terms of, the total number of retrieved oocytes and the number of metaphase II (MII) oocytes as well as the number of obtained and frozen embryos in the dual trigger group were significantly more than those of in the control group (P=0.001, P=0.022, P=0.01, and P=0.035, respectively). The clinical pregnancy and live birth rates in the dual group were higher than those of the control group; nevertheless, the differences were not statistically significant (40.9 vs. 25% and 40.9 vs. 20%, P=0.275 and P=0.143, respectively). By virtue of these findings, dual trigger significantly improved the ovarian stimulation outcomes in the patients with a history of unexpected poor response. To validate the current findings, further clinical trials with larger sample sizes are required (registration number: NCT04549649).

Endometriosis is a chronic inflammatory condition associated with debilitating chronic pelvic pain that affects women's quality of life. Several drugs have been used to reduce pain and psychological distress associated with this disease. Currently, gonadotropin-releasing hormone (GnRH) agonists and dienogest are the most widely used medical therapies for endometriosis.

This study aimed to investigate the efficacy of dienogest and GnRH agonists in improving pelvic pain after laparoscopic surgery for endometriosis.

In this randomized clinical trial study, 104 women with endometriosis who were referred to the Department of Reproductive Medicine of Yas hospital, Tehran, Iran, between April 2022 and March 2023 were studied. After laparoscopic surgery, individuals were randomly assigned into 2 groups (n = 52/each): the dienogest-administered group and the GnRH agonist-administered group. Participants were followed up at 3 months and pelvic pain was measured using the visual analog scale. Pelvic pain and adverse effects of drugs were compared between the groups.

Pelvic pain significantly improved in both treatment groups (p < 0.0001). No significant difference was observed in hot flashes and joint pain between the dienogest and GnRH agonist groups. However, a significant difference was found in vaginal dryness (p = 0.03) and decreased libido (p = 0.02). GnRH agonists and dienogest reduced irregular vaginal bleeding.

Our results suggested that the effect of GnRH agonists and dienogest in improving pelvic pain for endometriosis is the same after a 3-month treatment period. However, these 2 drugs caused different adverse effects.

Superovulation is a crucial component of assisted reproductive technology. Inducing superovulation with Gonadotropin-releasing hormone (GnRH) can lead to ovarian hyperstimulation, potentially affecting reproductive outcomes.

This study aimed to examine the effects of GnRH treatment on superovulation response and embryo recovery in Holstein heifers.

Twenty-one Holstein heifers (age: 135.15 months; weight: 361.05 kg) were selected based on their general health status and ovarian function. All heifers received two consecutive doses of prostaglandin F2α and underwent superovulation. The heifers were inseminated twice: Once at the onset of standing estrus and again 12 hours later. In the treatment group (13 heifers), a single dose of GnRH was administered simultaneously with the second insemination. The superovulation response was evaluated based on the number of corpus luteum (CL), unovulated follicles (UoF), total recovered embryos/ova, and the number of transferable embryos, using logistic regression with the GENMOD procedure in SAS.

The mean number of CL was not significantly greater in the control group (13.6) compared to the GnRH group (11.4). The average number of UoF was similar between the two groups (P = 0.1853). However, the control group had a significantly higher average total number of recovered embryos/ova (7.7) compared to the GnRH group (2.1). Additionally, the control group progesterone more transferable embryos, with an average of 2.5, while the GnRH group averaged 0.7 (P < 0.0062).

Gonadotropin-releasing hormone likely deactivated the oviduct by disrupting the balance of estradiol and estrogen, leading to a reduction in both the total number of embryos and the number of transferable embryos in heifers.

Despite the extensive use of the gonadotropin-releasing hormone (GnRH) antagonist protocol in treating infertile women, particularly those with polycystic ovary syndrome (PCOS), there have not been sufficient evidence to compare the flexible and fixed variants in in vitro fertilization (IVF) cycles.

This study aims to assess the treatment outcomes of flexible and fixed types of GnRH-antagonist protocol for IVF in women with PCOS.

In this randomized clinical trial, 150 infertile women with PCOS, who were candidates for IVF, and referred to the Yazd Research and Clinical Center for Infertility, Yazd, Iran between October 2023 and February 2024 were included. Participants were divided into 2 groups (n = 75/each) based on the type of antagonist protocol (fixed or flexible). GnRH antagonist administration started on the 5th day of gonadotropin treatment in the fixed group. In the flexible group when there was at least one follicle 12-14 mm, GnRH antagonist was started. Finally, the number of metaphase II oocyte, the quality of embryos, the duration of the stimulation cycle, the dose of gonadotropin, the number of GnRH-antagonist, and the rate of ovarian hyperstimulation syndrome were evaluated.

No statistically significant difference was observed in terms of cycle length and the total dose of gonadotropin between groups. Nevertheless, a notable distinction was observed in the total number of oocytes (17.84 vs. 15.5, p = 0.023) and mature oocytes (13.64 vs. 11.83, p = 0.019) in the flexible group compared to the fixed group.

In conclusion, the IVF outcomes are more favorable in women with PCOS undergoing the flexible GnRH-antagonist protocol compared to the fixed protocol.

Invasive angiomyxoma as a mesenchymal tumor with a high recurrence rate has been reported mainly in reproductive age according to its association with the estrogenic level of plasma. Above that, it seems there is a need for further treatment despite complete resection of the tumor, to eliminate the hormonal state. In the present study, we sought to introduce a rare case of invasive angiomyxoma in a post-menopausal but high-risk woman, discuss the relativity of risk factors in all hormonal-dependent gynecological malignancy, and intend to seek help from colleagues' opinions and experiences about treatment. It is clearly of great importance to emphasize the role of individualized medicine in such a rare case, in conclusion, there is not any debate on the role of surgical resection but the necessity of changing in lifestyle or adjuvant systemic or local therapy, and the needed duration is doubtful.

 Gonadotropin-releasing hormone acts on the anterior pituitary and promotes the release of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH), both of great importance in the ovarian cycle.

 In a prospective cross-sectional study conducted at the High Institute for Infertility Diagnosis and Assisted Reproductive Technologies / Al-Nahrain University and Kamal Al-Sameraie Hospital for Infertility and In Vitro Fertilization, Baghdad, Iraq during the period from April 2022 to April 2023, women received rFSH in a single daily dose of (150-300 IU) for ovarian stimulation. Women in groups B and C received ovarian stimulation antagonists, while those in group A did not.

 Both clinical and ongoing pregnancy rates were measured for each group. A positive hCG test was found in 27 (79.4%) in Group A while it was positive in 19 (55.9%) in Group B with a significant difference (P=0.03), clinical pregnancy was 25 (73.5%) in Group A while it was positive in 17 (50.0%) in Group B with a significant difference (P=0.04), and ongoing pregnancy was found in 24 (70.6%) in Group A while it was positive in 15 (44.1%) in Group B with significant difference (P=0.01).

Women with LH <4 IU presented with a significantly higher pregnancy rate than those with ≥4 IU, and do not need GnRH antagonist addition as co-treatment.

 There is no agreement on which of the 2 gonadotropin-releasing hormone (GnRH) agonist protocols are the most efficient, neither there is any consensus on which one yields a better clinical pregnancy percentage.

 The present study aims to compare the effectiveness of reduced dosages of long- and short-acting GnRH agonists on pregnancy outcomes.

 In this randomized controlled clinical trial, 400 women were randomly assigned to 2 groups (n = 200/group): the reduced dosage of long-acting GnRH agonist group (group 1, 1.25 mg Decapeptyl) and the short-acting GnRH agonist group (group 2, 0.5 mg/day Buserelin Acetate). The study was conducted at Mehr Medical Institute, Rasht, Iran between July 2019 and July 2020. Biochemical and clinical pregnancy were compared between groups.

 No significant differences were observed in the endometrial lining, the total number of retrieved and metaphase-II oocytes, progesterone, and serum estradiol levels on human chorionic gonadotropin day, fertilization rate, and top-quality embryos between the groups. The duration of induction (10.8 ± 1.7 vs. 10 ± 2.1, p < 0.001) and the total dosage of gonadotropins (2939.4 ± 945.9 vs. 2441 ± 1247.1, p < 0.001) were significantly greater in group 2 than in group 1. No significant differences were observed between the 2 groups in terms of implantation rate, chemical pregnancy rate, and clinical pregnancy rate. A higher percentage of ovarian hyperstimulation syndrome was observed in group 2 (p = 0.005).

 Due to a lower percentage of ovarian hyperstimulation syndrome in group 1 and similar assisted reproductive technology outcomes in both groups, the long protocol was found to be superior to the short protocol.

Selecting a suitable and preferable method for endometrial preparation in frozen embryo transfer (FET) cycles for women with adenomyosis is still challenging in infertility treatment.

To compare 2 artificial endometrial preparation regimens with and without gonadotropin-releasing hormone agonist (GnRHa) pretreatment in women with adenomyosis undergoing FET cycles.

This randomized clinical trial study was conducted on 140 adenomyosis cases who underwent FET cycles at Arash Women’s hospital, Tehran, Iran from May 2020 to March 2021. Participants were randomly allocated into hormonal replacement therapy (HRT) and HRT+GnRHa pretreatment groups (n = 70/each). Endometrial preparation with 2-6 mg daily estradiol was started in the HRT+GnRHa group, taking after down-regulation with the GnRHa. Within the HRT group, the same dose of estradiol was commenced within the early follicular stage. The main (chemical and clinical pregnancy rates) and auxiliary results (twin pregnancy, miscarriage, and live birth rates) were compared between groups.

The demographic characteristics and severity of adenomyosis, endometrial thickness, and pattern at starting progesterone administration were similar in the 2 groups, and triple-line endometrium was found to be the dominant pattern in both groups (p = 0.65). No significant differences were observed in chemical, clinical, and twin pregnancy rates as well as miscarriage and live birth rates between groups (p = 0.71, p = 0.81, p = 0.11, and p = 0.84, respectively). However, the total estrogen dose and duration of estrogen consumption were significantly higher in the pretreatment group (p = 0.001, and p = 0.003).

These results indicated that the hormonal endometrial preparation with estrogen and progestin for FET cycles is as efficacious as a protocol involving preceding pituitary suppression with a GnRHa. Further large randomized clinical studies are required to confirm these findings.

With the introduction of the dual triggering-gonadotropin-releasing hormone (GnRH) analog and recombinant human chorionic gonadotropin (hCG) combination, women with a history of low mature oocyte proportion and empty follicle syndrome were shown to benefit from the dual trigger.

To investigate whether dual triggering of oocyte maturation with a GnRH agonist (GnRHa) combined with hCG can affect the euploidy rate and improve in vitro fertilization outcomes for normoresponder women.

In this cross-sectional study, 494 women who underwent controlled ovarian stimulation with hCG (n = 274) or dual triggering (hCG+GnRHa, n = 220) at Acibadem Maslak hospital, Assisted Reproductive Unit, from January 2019-2022 were enrolled in this study. Preimplantation genetic testing for aneuploidy was performed on all participants.

Both groups had similar baseline and clinical characteristics. Of the 881 embryos biopsied, 312 (35.4%) were reported as euploid in the hCG trigger group; in the dual trigger group, 186 (29.8%) of 623 screening embryos were reported as euploid. The hCG group had a higher euploidy rate per biopsied embryo, although the difference was not statistically significant (31.4 ± 26.5 vs. 26.5 ± 33.3, p > 0.05).

In normoresponders, adding GnRHa for final follicular maturation to hCG did not improve the euploidy rate.

The adverse effect of chemotherapy on the proliferation of granulosa cells has been indicated in recent studies. Gonadotropinreleasing hormone (GnRH) antagonists exert protective effects on granulosa cells against the side effects of chemotherapy. In the present study, we aimed to evaluate the impact of cetrorelix on the proliferation of ovarian granulosa cells following administration of thiotepa in the ovaries of female mice.

In this experimental study, 30 adult Balb/c female mice (5-8 weeks old, weighing 24-28 g) were divided into three groups (n=10/ each group) (Control group, T. group, and C. group). T. group received 2.5 mg/kg of thiotepa for four consecutive days. The C. group received cetrorelix (0.25 mg/kg) before and at the same time as thiotepa administration and a week after the end of thiotepa administration. Ovaries were used for quantitative and immunohistochemical studies at the end of the investigation.

The mean numbers of follicles such as primordial, primary, secondary, and tertiary significantly decreased in the T. group than control group (P=0.02). Cetrorelix treatment exerted a protective effect against thiotepa-induced damage by increasing the mean numbers of follicles in the ovarian cortex (P=0.04).

As a GnRH antagonist, cetrorelix can be considered as one of the effective drugs to protect the granulosa cells against chemotherapy-induced damages in cancer disease.

The common causes of infertility in women with endometriosis are folliculogenesis alternation, steroidogenesis and fertilization impairment, oocyte and embryo quality reduction, and implantation defect.

To compare in vitro fertilization (IVF) cycle success rates of women with endometriosis who were treated with letrozole + gonadotropin (LA) vs. placebo + gonadotropin (PA).

This double-blind, randomized clinical trial study was conducted with 94 infertile women with endometriosis (47 in the LA group and 47 in the PA group) who were candidates for IVF, from April-June 2021. For all participants, the long agonist protocol was applied. In both groups, gonadotropin-releasing hormone agonist was prescribed in the mid-luteal stage and from the third day of the cycle, and gonadotropin was started and its doses were regulated based on the patient’s age, serum anti-Mullerian hormone and follicle-stimulating hormone. From the third day of the menstrual cycle, 5 mg of letrozole daily for 5 days prescribed for LA group, while placebo prescribed for PA on the identical days and duration. After embryo transfer, biochemical and clinical pregnancy were measured in the 2 groups.

The gonadotropin dosage (p < 0.01) and estradiol level (p = 0.02) on the human chorionic gonadotropin administration day were significantly lower in the LA group compared with in the PA group. Fetus transfer was done for 32 women. No significant differences were detected between the study groups regarding biochemical or clinical pregnancy (p = 0.72 for both).

Letrozole as a co-treatment drug in the IVF cycle of women with endometriosis can significantly reduce the gonadotropin dosage and estradiol level with the same pregnancy rates.

Despite prevalence of polycystic ovary syndrome (PCOS) among childbearing women and development of many animal models for this syndrome, information on its etiology is still scarce. The intrauterine hyperandrogenic environment may underlie changes at the level of hypothalamus, pituitary, ovary organization in female offspring, and PCOS later in life. Letrozole has been shown to mimic reproductive and metabolic characteristics of PCOS in adult rodent models. Therefore, this research aimed to assess the condition in a prenatal letrozole-treated rat model. 

Twenty-eight female rats dams receiving letrozole at certain doses during late pregnancy were used in the trial.  Pregnant Sprague-Dawley rats (n=21) received letrozole treatment on gestation days 16–18 at doses of 1.25, 1.0, 0.75, 0.5, and 0.25 mg/kg body weight (BW).    

Prenatal letrozole treatment delayed parturition time and reduced the litter size in pregnant dams (P<0.0001). Late puberty onset, irregular ovarian cyclicity, increased anogenital distance (AGD), body weight gain, serum testosterone concentration, and reduced estradiol levels (P<0.0001) were observed in the female offspring of dams receiving 1.25 and 1 mg/kg BW letrozole. Furthermore, letrozole at 1.25 and 1 mg/kg BW showed increased RFRP and decreased GnRH mRNA expression (P<0.0001). Letrozole treatment at doses of 1 mg/kg BW and lower was not fetotoxic. 

It was concluded that 1 mg/kg BW letrozole may be suggested for prenatal PCOS induction.

Analog triptorelin is one of the effective agonists for the treatment of reproductive disorders, particularly prostate cancer. Due to results of previous studies, we hypothesized that obsessive-compulsive disorder (OCD can be effectively treated with the long-term administration of a gonadotropin-releasing hormone (GnRH) analog, namely triptorelin. The aim of this study was to evaluate the effectiveness of triptorelin injection in clientswith OCD.

This randomized single-blind clinical trial was performed on 30 clientswith OCD who had a Yale-Brown score of > 17 after 8 weeks of treatment. The participants were randomly assigned into twogroups of triptorelin and placebo. The clientsin the intervention group were treated with Selective serotonin reuptake inhibitors (SSRIs), includingfluoxetine, in addition to triptorelin threetimes a month for at least 8 weeks. Clientsin the control group received injection of distilled water as placebo threetimes in addition to the routine treatment. The outcome was evaluated by Yale-Brown OCD scale (Y-BOCS) at the baseline, as well as 4, 8, and, 20 weeks after the end of the treatment.

The mean scores of Y-BOCS in the intervention and control groups was 30.5 ±67.6 and 30.5 ±67.6, respectively, before intervention, indicating no significant difference between the twogroups (P = 0.0.8). The comparison of Y-BOCS scores after the intervention showed a significant difference between the twogroups in the scores 4 (P = 0.01), 8 (P < 0.005), and 20 (P < 0.005) weeks after the treatment. With regards to the side effects of the medicine, 6.7% (n = 1) of the clientsin the control group developed headache and 66.7% (n = 10) had late period in intervention group. The results revealed a significant difference between the twogroups in terms of side effects (P < 0.005).

The results of this study showed triptorelin decreased the symptomsof OCD. The effectiveness of triptorelin in the treatment of symptoms in clientswith OCD was confirmed in our study. However, due to the limited research addressing this domain, future studies are suggested to clarify this conclusion.

Targeted drug delivery is a novel method to specifically deliver anticancer therapeutics to tumor sites. Gonadotropin-releasing hormone (GnRH) is a decapeptide, and its target binding property has attracted attention as a means of targeted drug delivery. Human pancreatic ribonuclease 1 (hpRNase1) has been shown to exert anticancer properties, when fused to a targeting moiety. The goal of the present study was to add a GnRH targeting peptide to the N-terminus of hpRNase1 to specifically target GnRH receptor (GnRH-R) expressing cells. This in vitro study was conducted at Shiraz Institute for Cancer Research (Shiraz, Iran) in 2019. The coding sequence of GnRH and hpRNase1 were fused, and the chimeric protein together with non-fused hpRNase1 were produced in E. coli (BL21). The recombinant proteins were purified, and their biological activity was evaluated using MTT and apoptosis assays. Non-parametric Kruskal–Wallis tests with Dunn’s post hoc tests were performed to determine the significant differences between the study groups. GnRH-hpRNase1 chimeric protein specifically inhibited the proliferation of PC-3 (P=0.021), LNCaP (P=0.034), and AD-Gn (P=0.041) cells, while the growth of negative cells (AD-293) was not significantly affected (P=0.081). GnRH-hpRNase1 decreased the IC50 values more than non-fused hpRNase1, by approximately 26.5-fold (P=0.036) for PC-3 cells, and exerted its growth inhibitory effects through apoptosis induction. Fusion of GnRH to hpRNase1 structure produced an enzyme, which could specifically target tumor cells. This approach can be used to eliminate tumors that harbor GnRH-R.

A repeat dose of Gonadotropin-releasing Hormone (GnRH) agonist could provide long duration of luteinizing hormone (LH) surge and amplitude appropriately.

Improvement in oocyte maturity could be obtained by a repeat dose of GnRH agonist.

In this randomized double-blinded study, 120 women with polycystic ovarian syndrome and serum estradiol level (E2) > 3000 who were candidate for in vitro fertilization with Antagonist protocol were enrolled between July 2018 and July 2019.  Participants were randomized in two groups - and final oocyte maturation was triggered with two doses: In group A, a repeat dose of 0.1 mg, 12 hr. after the first dose and in group B, 0.2 mg SC triptorelin (decapeptyl) 35 hr. prior to oocyte retrieval. Serum Estradiol, LH, and progesterone concentration were measured on the trigger day. Serum LH measurement was done three times in both groups. The outcomes were oocyte yield, meiosis (M) I, MII, Maturity rate, germinal vesicle (GV) rate, 2 pronuclear, embryo yield, ovarian hyper stimulation syndrome rates.

Maturity rate (p= 0.89), MI (p= 0.38), MII (p= 0.89), and GV oocytes (p= 0.38) were not statistically different between the two study groups. LH levels measured at 12 hr post-trigger did not relate statistically significant with maturity rate in our participants (p= 0.96). No empty follicular syndrome was reported.

Although, the second dose of GnRH agonist after 12 hr since the first dose could provide duration of LH surge and amplitude and as a result no empty follicular syndrome was seen, the maturity rate, MI, MII, and GV oocytes were not different between the two study groups.

Preparation of endometrial thickness in frozen-thawed embryo transfer (FET) is extremely important, particularly in repeated implantation failure (RIF) patients.

This study aimed to investigate the clinical outcomes of FET cycles among RIF women, based on the effects of administering gonadotropin-releasing hormone (GnRH) agonist prior to estrogen-progesterone preparation of the endometrium.

In this randomized clinical trial, 67 infertile women who were candidates for FET were divided into two groups: A) case group (n = 34), treated with GnRH agonist prior to endometrial preparation and B) control group (n = 33), which received the routine protocol.(6 mg daily estradiol started from second day) The clinical outcomes including chemical and clinical pregnancy, in addition to implantation rates, were compared between the two groups.  

The results showed no significant differences in women’s age (p = 0.558), duration (p = 0.540), type (p = 0.562), and cause of infertility (p = 0.699). Regarding pregnancy and implantation rates, there was a trend toward an increase in the case group; however, differences were not statistically significant.

Although our results showed no significant differences between groups. Because there are trends to better results in case group larger sample size may show significant difference.

There are conflicting results regarding the benefit of gonadotropin releasing hormone (GnRH) agonist treatment on frozen embryo transfer (FET) outcome. No study was found to compare pregnancy outcome between patients undergoing short and long acting types of GnRH agonist for FET cycles. This study aimed to assess the effectiveness of short and long acting GnRH agonist on FET cycle outcomes.

The present retrospective study was conducted on 296 patients who underwent FET cycles between 2016 and 2017 at Mehr Medical Institute, Rasht, Iran. Pregnancy outcome were compared among three groups: Group A (n=103) received artificial hormone-mediated cycles without GnRH agonists, Group B (n=100) and C (n=93) received artificial hormone-mediated cycles with short and long-acting GnRH agonists, respectively. Also 16, 26, 12 polycystic ovarian syndrome (PCOS) patients (in group A, B and C respectively) were also assessed for ongoing pregnancy rate among three groups. Data were analyzed using analysis of variance, Kruskal-Wallis, Chi-square goodness of fit test and multivariate logistic regression.

No statistically significant differences were observed in terms of endometrial thickness (p=0.053), implantation (p=0.94), biochemical (p=0.67), clinical (p=0.82) and ongoing (p=0.96) pregnancy rates in three groups. Also, PCOS patients did not show significant differences in ongoing pregnancy rate among three groups (p=0.72).

The findings revealed that neither non- PCOS nor PCOS patients undergoing artificial hormone-mediated endometrial preparation benefit from the addition of short or long-acting GnRH agonist to FET cycles.

The purpose of this study was to compare the effects of Glycyrrhiza glabra (Licorice), a cyclooxyge- nase-2 inhibitor (Celecoxib) and a gonadotropin-releasing hormone analog (Diphereline®), with a control group on endometrial implants in rats. In this experimental study, endometriosis was induced in rats by auto transplantation and after confirmation, the rats were divided into 4 groups that were treated for 6 weeks with normal saline (0.5 ml/day, orally), licorice extract (3000 mg/kg/day, orally), celecoxib (50 mg/kg, twice a day, orally) or diphereline (3 mg/kg, intramuscularly). At the end of treatments, the mean area, volume, histopathology and hemosiderin-laden macrophage (HLM) counts of the endometrial implants were evaluated and compared among the four groups. The mean area, volume and HLM counts of the implants in the licorice group were significantly lower than those of the control group (P<0.001). The histopathologic grades of endometrial implants were significantly decreased by licorice compared to the control group (P<0.001). There was no significant change in the mentioned parameters in rats treated with celecoxib compared to the control group. Diphereline was the most potent agent for suppressing the growth of endometrial implants in terms of all of the above-mentioned parameters. Licorice decreased the growth and histopathologic grades of auto-transplanted endometrial implants. However, while celcoxib had no significant effect, diphereline showed the highest potency for decreasing the endome- trial growth. Licorice may have the potential to be used as an alternative medication for the treatment of endometriosis.