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OBJECTIVE: To determine the localization, expression, and function of Toll-like receptors (TLRs) in fallopian tube epithelial cells. METHODS: The localization of TLRs in fallopian tube epithelial cells was investigated by immunostaining. Surprisingly, the intensity of staining was not equal in the secretory and ciliated cells. After primary cell culture of fallopian tube epithelial cells, ring cloning was used to isolate colonies of ciliated epithelial cells, distinct from non-ciliated epithelial cells. The expression of TLRs 1–10 was examined by quantitative real-time polymerase chain reaction, and protein localization was confirmed by immunostaining. The function of the TLRs was determined by interleukin (IL)-6 and IL-8 production in response to TLR2, TLR3, TLR5, TLR7, and TLR9 ligands. RESULTS: Fallopian tube epithelial cells expressed TLRs 1–10 in a cell-type-specific manner. Exposing fallopian tube epithelial cells to TLR2, TLR3, TLR5, TLR7, and TLR9 agonists induced the secretion of proinflammatory cytokines such as IL-6 and IL-8. CONCLUSION: Our findings suggest that TLR expression in the fallopian tubes is cell-type-specific. According to our results, ciliated cells may play more effective role than non-ciliated cells in the innate immune defense of the fallopian tubes, and in interactions with gametes and embryos.
Subject(s)
Female , Humans , Clone Cells , Cloning, Organism , Cytokines , Embryonic Structures , Epithelial Cells , Fallopian Tubes , Germ Cells , Interleukin-6 , Interleukin-8 , Interleukins , Ligands , Primary Cell Culture , Real-Time Polymerase Chain Reaction , Toll-Like ReceptorsABSTRACT
Background: Endometriosis is a prevalent gynecological disease, with limited known etiology and more researches are required to identify its etiology. In this manner, there is no evidence for expression and function of 3and acute;HOX genes in 4 clusters in the limb and pelvic organs such as the uterus and its disorders [Genes in the HOXA-D clusters are subdivided into 13 paralogous groups]
Objective: This study designed to investigate the expression profile of 5 paralogous [1-5] in four clusters of HOX genes [A, B, C, and D] in ectopic and eutopic tissues of women with endometriosis compared to the normal endometrium
Materials and Methods: Samples were obtained from thirty patients [15 with and 15 without endometriosis] of reproductive age with normal menstrual cycles. The same patient provided both eutopic and ectopic tissues and control women were laparoscopically checked for the absence of endometriosis. The expression profile of these HOX genes was investigated by quantitative real-time polymerase chain reaction technique
Results: We observed significant up-regulation of some members of HOXC and D clusters [HOXD1, HOXD3, HOXC4 and HOXC5] in ectopic and eutopic tissues vs. control. Also, our data showed significant down-regulation of all of HOXA and HOXB paralogous except HOXA1 in ectopic tissues versus control
Conclusion: Our data showed specific cluster dependent modulation of the HOX genes expression in endometriosis [over-expression of some HOX genes in cluster C and D and down-regulation of HOX genes in cluster A and B] in ectopic and eutopic tissues compare to control group. Therefore, it is possible that change of expression level of these genes in endometrium plays a role in the pathogenesis of endometriosis
ABSTRACT
As numerical and structural defects in chromosomes are an inevitable consequence of IVF, Pre-implantation genetic diagnosis and screening [PGD/PGS] methods are used for detecting abnormalities in embryos before implantation to the uterus to increase the successful rate of IVF. Pre-implantation genetic diagnosis and screening approaches can be achieved by different techniques such as NGS, CGH and FISH. Among these approaches, FISH-based PGD/PGS is challenging in that it requires experience and skill to increase its facility and validity. Therefore, based on literature review and our experiences obtained from genetic laboratory of Yazd Reproductive Sciences Institute [Yazd, Iran], we were ditermined to discuss these challenges. After reviewing the available protocols and articles, we compared results of different methods for performing pre- and post-examination FISH process. Required samples in each section were obtained from embryo in cleavage or blastocyst stage. According to our team's experience, we recommend the cleavage stage biopsy and our modified fixation method. Also, we do not recommend more than two round hybridization on the same cell. Many studies have shown that FISH-based PGD is an efficient method for decreasing IVF failure in infertile patients. This paper introduces the best biopsy and fixation method and, includes some useful tips and tricks on type and number of probe, removing the cytoplasm, denaturation and hybridization, data evaluation and scoring criteria
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Background: Anti-Mullerian hormone [AMH] is considered as a good marker for quantitative evaluation of ovarian response to the stimulation during assisted reproductive technology cycles
Objective: to evaluate the association between serum AMH level and embryo morphokinetics using time-lapse imaging and intracytoplasmic sperm injection [ICSI] outcomes in women with polycystic ovarian syndrome [PCOS]
Materials and Methods: we evaluated a total of 547 embryos from 100 women underwent ICSI cycles; 50 women with PCOS and 50 women with tubal factor infertility. Serum AMH level was measured in all participants. Time-laps records were annotated for time to pronuclear fading [tPNf], time to 2-8 cells [t2-t8], reverse cleavage, direct cleavage, and also for the presence of multinucleation
Results: AMH was negatively correlated with t5, t8, and the third cell cycle [p=0.02, p=0.02, and p=0.01; respectively] in PCOS group. AMH had no correlation with embryo kinetics in infertile women with tubal factor infertility. Moreover, AMH level is similar between embryos with and without direct cleavage as well as reverse cleavage and Multinucleation in both groups. The Receiver operating characteristic curves analyses indicated that AMH was not an accurate predictor of clinical pregnancy as well as a live birth [AUC=0.59 [95% CI, 0.42-0.76]] in PCOS women. However, in the women with tubal factor infertility AMH showed a fair prediction value for clinical pregnancy [AUC=0.64 [95% CI, 0.48-0.82]] along with the live birth [AUC=0.70 [95% CI, 0.55-0.85]]
Conclusion: some of the time-lapse embryo parameters may be related to the AMH concentration. However, AMH is not an accurate tool to predict the ICSI outcomes in PCOS women
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Background: Endometriosis is a disease that affects women of reproductive age. This disease is characterized by the presence of endometrial-like tissues [endometrial or stromal glands] outside the uterus and shows significantly elevated prevalence in industrial regions. Additionally, an interaction between genetics and environmental factors is assumed for the disease. Enzymes belonging to the cytochrome P450 [CYP] family are participated in detoxi?cation process of a wide range of environmental toxins and carcinogens. Thereby, they are good link for the interaction. CYP1A1 which belong to cytochrome P450 [CYPs] superfamily, is a very important gene for the metabolism of carcinogens
Objective: The aim of this study was to analyze the frequency of the MspI polymorphism of CYP1A1 gene and its relation to endometriosis
Materials and Methods: Genomic DNA was isolated from 93 endometriosis women and 139 healthy controls. Genotyping was performed using polymerase chain reaction followed by restriction fragment length polymorphism analysis
Results: Frequencies of the TT, TC, and CC genotype of CYP1A1 gene polymorphism in patients were 73.1 percent, 22.6 percent, and 4.3 percent, while frequencies in controls were 74.1 percent, 22.3 percent, and 3.6 percent, respectively. So there was no significant differences between the genotypes in two groups [p=0.961]
Conclusion: According to our study, MspI polymorphism of CYP1A1 gene appears to be not associated with the risk of endometriosis in the studied population. However, additional studies, especially with larger sample size are needed to validate these findings
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Background: The use of embryo cryopreservation excludes the possible detrimental effects of ovarian stimulation on the endometrium, and higher reproductive outcomes following this policy have been reported. Moreover, gonadotropin-releasing hormone agonist trigger in gonadotropin-releasing hormone [GnRH] antagonist cycles as a substitute for standard human chorionic gonadotropin trigger, minimizes the risk of ovarian hyperstimulation syndrome [OHSS] in fresh as well as frozen embryo transfer cycles [FET]
Objective: To compare the reproductive outcomes and risk of OHSS in fresh vs frozen embryo transfer in high responder patients, undergoing in vitro fertilization triggered with a bolus of GnRH agonist
Materials and Methods: In this randomized, multi-centre study, 121 women undergoing FET and 119 women undergoing fresh ET were investigated as regards clinical pregnancy as the primary outcome and the chemical pregnancy, live birth, OHSS development, and perinatal data as secondary outcomes
Results: There were no significant differences between FET and fresh groups regarding chemical [46.4% vs. 40.2%, p=0.352], clinical [35.8% vs. 38.3%, p=0.699], and ongoing [30.3% vs. 32.7%, p=0.700] pregnancy rates, also live birth [30.3% vs. 29.9%, p=0.953], perinatal outcomes, and OHSS development [35.6% vs. 42.9%, p=0.337]. No woman developed severe OHSS and no one required admission to hospital
Conclusion: Our findings suggest that GnRHa trigger followed by fresh transfer with modified luteal phase support in terms of a small human chorionic gonadotropin bolus is a good strategy to secure good live birth rates and a low risk of clinically relevant OHSS development in in vitro fertilization patients at risk of OHSS
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Background: management of poor-responding patients is still major challenge in assisted reproductive techniques [ART]. Delayed-start GnRH antagonist protocol is recommended to these patients, but little is known in this regards
Objective: the goal of this study was assessment of delayed-start GnRH antagonist protocol in poor responders, and in vitro fertilization [IVF] outcomes
Materials and Methods: this randomized clinical trial included sixty infertile women with Bologna criteria for ovarian poor responders who were candidate for IVF. In case group [n=30], delayed-start GnRH antagonist protocol administered estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation with gonadotropin. Control group [n=30] treated with estrogen priming antagonist protocol. Finally, endometrial thickness, the rates of oocytes maturation,, embryo formation, and pregnancy were compared between two groups
Results: rates of implantation, chemical, clinical, and ongoing pregnancy in delayed-start cycles were higher although was not statistically significant. Endometrial thickness was significantly higher in case group. There were no statistically significant differences in the rates of oocyte maturation, embryo formation, and IVF outcomes between two groups
Conclusion: there is no significant difference between delayed-start GnRH antagonist protocols versus GnRH antagonist protocol
ABSTRACT
Background: Despite of higher pregnancy rate after frozen embryo transfer [FET] which is accepted by the majority of researches, the safety of this method and its effect on neonatal outcome is still under debate
Objective: The aim of this study was to evaluate pregnancy and neonatal outcome of FET compare to fresh cycles
Materials and Methods: In this study,1134 patients using fresh ET and 285 women underwent FET were investigated regarding live birth as primary outcome and gestational age, birth weight, gender, multiple status, ectopic pregnancy, still birth and pregnancy loss as secondary outcomes
Results: Our results showed that there is no difference between FET and fresh cycles regarding live birth [65.6% vs. 70.4% respectively]. Ectopic pregnancy, still birth and abortion were similar in both groups. The mean gestational age was significantly lower among singletons in FET group compared to fresh cycles [p=0.047]. Prematurity was significantly elevated among singleton infants in FET group [19.6%] in comparison to neonates born after fresh ET [12.8%] [p=0.037]
Conclusion: It seems that there is no major difference regarding perinatal outcome between fresh and frozen embryo transfer. Although, live birth is slightly increased in fresh cycles and prematurity was significantly increased among singleton infants in FET group
ABSTRACT
Objective: Toll like receptors [TLRs] are one of the main components of the innate im-mune system. It has been reported that expression of these receptors are altered in the female reproductive tract [FRT] during menstrual cycle. Here we used a fallopian tube epithelial cell line [OE-E6/E7] to evaluate the effect of two sex hormones in modulating TLR expression
Materials and Methods: In this experimental study, initially TLR gene expression in OE-E6/E7 cells was evaluated and compared with that of fallopian tube tissue using quantitative real time-polymerase chain reaction [qRT-PCR] and immunostaining. Thereafter, OE-E6/E7 cells were cultured with different concentrations of estradiol and progesterone, and combination of both. qRT-PCR was performed to reveal any changes in expression of TLR genes as a result of hormonal treatment
Results: TLR1-10 genes were expressed in human fallopian tube tissue. TLR1-6 genes and their respective proteins were expressed in the OE-E6/E7 cell line. Although estradiol and progesterone separately had no significant effect on TLR expression, their combined treatment altered the expression of TLRs in this cell line. Also, the pattern of TLR expression in preovulation [P], mensturation [M] and window of implantation [W] were the same for all TLRs with no significant differences between P, M and W groups
Conclusion: These data show the significant involvement of the combination of estradiol and progesterone in modulation of TLR gene expression in this human fallopian tube cell line. Further experiments may reveal the regulatory mechanism and signalling pathway behind the effect of sex hormones in modulating TLRs in the human FRT
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Background: Implantation failure is one of the most important factors limiting success in IVF treatment. The majority of trials have demonstrated favorable effect of endometrial injury on implantation success rate especially in women with recurrent implantation failure, while some studies failed to detect any benefit
Objective: The purpose of our trial was to explore whether endometrial injury in luteal phase prior to frozen-thawed embryo transfer cycles would improve pregnancy outcomes?
Materials and Methods: We conducted a prospective controlled trial of 93 consecutive subjects at a research and clinical center for infertility. All women were undergone frozen-thawed embryo transfer [FTE] cycles. Women in the experimental group underwent endometrial biopsy with a Pipelle catheter in luteal phase proceeding FET cycle. Primary outcomes were implantation and clinical pregnancy rates and secondary outcomes were chemical, ongoing and multiple pregnancy and miscarriage rates
Results: 45 subjects who underwent endometrial injury [EI] were compared with 48 control group which did not include any uterine manipulation. There were no significant differences in baseline and cycle characteristics between two groups. The difference in implantation rate was trend to statistically significance, 11.8% in EI group vs. 20.5% in control group [p=0.091]. The chemical, clinical and ongoing pregnancy rates were lower in EI group compared with control group but not statistically significant. The multiple pregnancy rate and miscarriage rate also were lower in EI group compared with control group
Conclusion: Based on results of this study, local injury to endometrium in luteal phase prior to FET cycle had a negative impact on implantation and clinical pregnancy rates
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This paper summarizes the proceedings of a 1 day national symposium entitled "Reproductive biology, stem cells biotechnology and regenerative medicine" held at Shahid Sadoughi University of Medical Sciences, Yazd, Iran on 3[rd] March 2016. Here, we collected the papers that presented and discussed at this meeting by specialists that currently researched about the overlaps of the fields of reproductive biology and stem cells and their applications in regenerative medicine
ABSTRACT
Background: Serum concentrations of antimullerian hormone [AMH] correlate with ovarian response during assisted reproduction treatment [ART] cycles
Objective: This retrospective study attempted to evaluate the selection of ovarian stimulation protocols based on serum AMH levels in patients and its impact on the results of ART
Materials and Methods: Based on AMH levels, the patients with tubal factor infertility were divided in three groups of normal, low and high AMH levels. Oocyte, good embryo number and pregnancy rate in each group were analyzed
Results: Using agonist and antagonist protocols, an increase in serum AMH led to higher number of oocytes and better quality embryos. At all low, normal and high AMH levels, the agonist protocol led to a more significant increase in the number of oocytes than the antagonist protocol [p<0.05]. The number of high quality embryos significantly increased by the agonist protocol than antagonist protocol in women with normal AMH levels of 1.3-2.6 ng/ml [p=0.00]. Moreover, the results for the number of high quality embryos at AMH >2.6 ng/ml was in favor of the antagonist protocol [p=0.00]. The results showed the lowest pregnancy rate at AMH <1.3 ng/ml. At AMH >2.6 ng/ml, there was a significant increase in pregnancy rate through the antagonist protocol [p=0.04]
Conclusion: Findings of this study suggested that the ART results are predictable, taking into account the AMH levels. The protocol specific to each patient can be used given the AMH level in each individual. This is because the results of each protocol depend on individual conditions
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Background: Genital tuberculosis [GTB] is an important cause of female infertility, especially in developing countries. The positive results of polymerase chain reaction [PCR] in endometrial GTB in the absence of tubal damage raise the possibility of the detection of sub-clinical or latent disease, with doubtful benefits of treatment
Objective: To evaluate the mycobacterium tuberculosis infection in endometrial biopsy samples collected from unexplained infertile women attending Yazd Research and Clinical Center for Infertility by using PCR techniques
Materials and Methods: In this cross sectional study, 144 infertile women with unexplained infertility aged 20-35 years old and normal 1-listro-saplango graphy findinus were enrolled. Endometrial biopsy samples from each participant were tested fbr mycobacterium tuberculosis detecting by PCR. In 93 patients, peritoneal fluid was also taken for culture and PCR
Results: The PCR results of endometrial specimens were negative in all cases, demonstrating that there was no GTB infection among our patients
Conclusion: Our results showed that GTB could not he considered as a major problem in women with unexplained infertility. Although, studies have indicated that PCR is a useful method in diagnosing early GTB disease in infertile women with no demonstrable evidence of tubal or endometrial involvement
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Recurrent pregnancy loss [RPL] has been defined as two or more miscarriages before 20[th] week of gestation. It seems that IL-27 may reduce inflammatory responses and affect the survival of the embryo during human pregnancy. IL-27 polymorphisms may influence RPL by altering the levels or the activity of gene product. We studied for the first time the association of IL-27 -964 A>G single nucleotide polymorphism [SNP] with RPL in Iranian women. A case-controlled study was performed on two groups consisting of 150 healthy women with at least one delivery [control group] and 150 women with two or more primary RPLs history [RPL group]. The -964 A>G SNP in IL-27 gene was determined by PCR-RFLP technique. Genotype and allele frequencies were compared using Chi[2] tests between two groups. There was no difference between the two groups regarding age of women [29 +/- 4.4 [control] vs. 30.84 +/- 5.2 years [case]]. In the RPL group, the genotype frequencies of -964 A>G polymorphism were AG [49.3%], AA [40%], and GG [10.7%], and in the control group, they were AG [43.3%], AA [48.7%], and GG [8%]. There was no significant difference between the genotypes of AA, AG, and GG in two groups [p=0.23]. As the frequency of allele A was 64.7% in the RPL group and 70.3% in the control group, the difference in frequency of allele A in -964 A>G between two groups was not significant [p=0.19]. Our findings indicate that SNP of -964 A>G in IL-27 gene is not a risk factor for RPL in Iranian women
Subject(s)
Humans , Female , Cytokines , Abortion, Habitual , Interleukin-27 , Case-Control Studies , Pregnant WomenABSTRACT
Recently, motile sperm organelle morphology examination [MSOME] criteria as a new real time tool for evaluation of spermatozoa in intracytoplasmic sperm injection [ICSI] cycles has been considered. The aim was to investigate the predictive value of MSOME in in vitro fertilization [IVF] in comparison to ICSI cycles and evaluation of the association between MSOME parameters and traditional sperm parameters in both groups. This is a cross sectional prospective analysis of MSOME parameters in IVF [n=31] and ICSI cycles [n=35]. MSOME parameters were also evaluated as the presence of vacuole [none, small, medium, large or mix]; head size [normal, small or large]; cytoplasmic droplet; head shape and acrosome normality. In sub-analysis, MSOME parameters were compared between two groups with successful or failed clinical pregnancy in each group. In IVF group, the rate of large nuclear vacuole showed significant increase in failed as compared to successful pregnancies [13.81 +/- 9.7vs7.38 +/- 4.4, respectively, p=0.045] while MSOME parameters were the same between successful and failed pregnancies in ICSI group. Moreover, a negative correlation was noticed between LNV and sperm shape normalcy. In ICSI group, a negative correlation was established between cytoplasmic droplet and sperm shape normalcy. In addition, there was a positive correlation between sperm shape normalcy and non-vacuolated spermatozoa. The high rate of large nuclear vacuoles in sperm used in IVF cycles with failed pregnancies confirms that MSOME, is a helpful tool for fine sperm morphology assessment, and its application may enhance the assisted reproduction technology success rates
Subject(s)
Adult , Female , Humans , Male , Cross-Sectional Studies , Prospective Studies , Sperm Injections, Intracytoplasmic , Pregnancy Rate , Sperm Head , Spermatozoa , VacuolesABSTRACT
The human female reproductive tract [FRT] is constantly deal with the invading pathogens. Recognition of these pathogens is attributed to the family of Toll like receptors [TLR] as a major part of the innate immune system. We and others have previously revealed that TLRs1-6 express in the female reproductive tract. However, more studies should be done to detect TLRs 7-10 in the female reproductive tract, especially in the fallopian tubes. To examine the expression of TLRs7-10 in human fallopian tube tissue. Using immunostaining techniques, distribution of TLR7-10 was studied in surgical sections from the uterine tubes, obtained from patients undergoing tubal ligation and hysterectomy for benign gynecological conditions. RT-PCR was used to show the existence of TLR7-10 genes in fallopian tube tissue. TLR7-10 proteins were detected in the fallopian tube epithelium, although the intensity of staining was not equal in cases. TLR7-10 genes were expressed in human fallopian tube tissue. This study indicates that TLR7-10 is expressed in fallopian tubes tissues, and may play an important role in microbial recognition, and in host defense against ascending infection
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Increased serum progesterone on the day of human chorionic gonadotropin administration may affect in vitro fertilization [IVF] outcome. The aim of this study was to evaluate whether progesterone elevation on the day of human chorionic gonadotropin administration is associated with poor IVF outcome. To determine the relationship between serum progesterone on the day of HCG and the outcome of IVF-embryo transfer treatment, 378 infertile patients undergoing IVF-embryo transfer at Yazd Research and Clinical Center for Infertility from October 2009 to March 2011 were prospectively studied. In this study, absolute p-value and P/E[2] ratio were not a good predictor outcome of in-vitro fertilization but progesterone per metaphase II were predictive of implantation rate and pregnancy rate with statistically significant results but had no effect on the fertilization rate. We suggest avoided the increased progesterone that the cause of advanced endometrial maturation and impaired endometrial receptivity. If the progesterone is greater than 0.32 per oocyte metaphase II, the embryo transfer can be canceled and freezing all embryos for future transfer must be considered, to increase acceptance of the endometrium and thus increase the success rate
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Frozen- thawed embryo transfer is an essential part of ART treatment and outcomes of this procedure are associated with several clinical factors. Several studies have showed an increase level of IVF outcomes in women with sufficient vitamin D. whether treatment of vitamin D insufficiency can improve pregnancy rates in frozen-thawed embryo transfer cycles. This is an interventional, randomized clinical trial. Serum 25-[OH] vitamin D level of 128 women who had undergone IVF/ICSI with cryopreservation of embryos was checked. One hundred fourteen infertile women with insufficient serum vitamin D [less than 30 ng/ml] were included in the study. Fifty seven women were treated with supplementary vitamin D, 50000 IU weekly, for 6-8 weeks and fifty seven women were received no supplementation. One hundred six women completed frozen thawed embryo transfer cycles and included in the final analysis. Primary and secondary outcomes were chemical and clinical pregnancy respectively. Our study did not show any significant difference between vitamin D insufficient and treated women in term of chemical [29.40% vs. 29.10% respectively, p=1.00] or clinical [25.50% vs. 21.80% respectively, p=0.81] pregnancy rates. Vitamin D insufficiency treatment is not associated with higher pregnancy rate in frozen-thawed embryo transfer cycles
Subject(s)
Humans , Female , Embryo Transfer , Fertility , Pregnancy , Pregnancy RateABSTRACT
Using aspirin, heparin, or both in women with unexplained recurrent miscarriage could be useful, because this problem might be initiated by thrombosis in decidual vessels. To investigate the association between thrombophilia and unexplained recurrent miscarriage and to evaluate the efficacy of anticoagulant treatment. In this quasi experimental, we enrolled 520 women, who had a history of recurrent miscarriage. Two hundred fifty two women with unexplained recurrent miscarriage were assigned to receive aspirin [80 mg daily] for two month before pregnancy and after confirmation of a viable pregnancy until 36 weeks of gestation or receive aspirin, as the same, plus heparin [5000 unit twice a day] subcutaneously after confirmation of viable pregnancy until 4 weeks after delivery. Type of medication was chosen for each woman according to number of abortion and age. Live-birth rates did not different significantly among the two study groups. The proportions of women who gave birth to a live normal infant were 74.5% in the group receiving aspirin plus heparin [combination-therapy group] and 79.8% in the aspirin group. Live-birth rates did not different significantly among the two study groups. So, using aspirin or aspirin plus heparin did not change pregnancy rate in these patients. Using aspirin is easier than injecting heparin which should be chosen case by case
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Background: Some trials have compared laparoscopic ovarian drilling [LOD] with gonadotropins but, because of variations in study design and small sample size, the results are inconsistent and definitive conclusions about the relative efficacy of LOD and gonadotropins cannot be extracted from the individual studies
Objective: To evaluate the relative efficacy of LOD and gonadotropins for infertile women with clomiphene citrate- resistant poly cystic ovary syndrome [PCOS]
Materials and Methods: A complete electronic literature search in databases including EMBASE, MEDLINE, Cochrane Library and Google scholar for some specific keywords was accomplished. We contained randomized clinical trials comparing outcomes between LOD, without medical ovulation induction, and gonadotropins
Results: Six trials, covering 499 women, reported on the primary outcome of pregnancy rate. There was no evidence of a difference in pregnancy rate when LOD compared with gonadotropins [OR: 0.534; 95% CI: 0.242-1.176, p=0.119, 6 trials, 499 women, I2=73.201%]. There was evidence of significantly fewer live births following LOD compared with gonadotropin [OR: 0.446; 95% CI: 0.269-0.74, p=0.02, 3 trials, 318 women, I2=3.353%]. The rate of multiple pregnancies was significantly lower in the LOD arm compared to the gonadotropins arm [OR: 0.127; 95% CI: 0.028-0.579, p=0.008, 3 trials, 307 women, I2=0%]
Conclusion: Our result revealed that there was no evidence of a significant difference in rates of clinical pregnancy and miscarriage in women with clomiphene citrate-resistant PCOS undergoing LOD compared to the gonadotropin arm. The decrease in multiple pregnancies rate in women undergoing LOD makes this option attractive. The increase in live birth rate in the gonadotropin group may be because of the higher rate of multiple pregnancies in these women. However, more focus on the long-term effects of LOD on ovarian function is suggested