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Objective@#This retrospective study aimed to investigate the prevalence of chronic endometritis, diagnosed using CD138 immunohistochemistry, among infertile women and to assess the association between chronic endometritis and recurrent implantation failure (RIF). @*Methods@#In total, 266 patients who underwent hysteroscopy due to infertility between 2019 and 2020 were included in the analysis. Of these, 136 patients with RIF and 130 non-RIF patients were included in the study. CD138 immunohistochemistry test results, blood biomarkers (including natural killer cells, white blood cells, and the lymphocyte-to-neutrophil ratio), and data on pregnancy outcomes were obtained. If the CD138 test yielded a positive result, the patients received antibiotic treatment. @*Results@#The overall proportion of CD138-positive patients was 32.7% (87/266). The CD138 positivity rate was not related to the number of cycles with implantation failure. In the RIF patient group, no significant associations were found between CD138 positivity and peripheral blood markers. The clinical pregnancy rates were similar between infertile women treated with antibiotics for chronic endometritis and those without chronic endometritis. @*Conclusion@#To improve the pregnancy rate in infertile patients, it may be helpful to combine CD138 testing with other laboratory tests and administer antibiotic treatment if the result is positive.
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This article reports the live birth of a healthy newborn using vitrified-warmed oocytes from fertility preservation before ovarian surgery. The patient in our case underwent two cycles of controlled ovarian stimulation before laparoscopic bilateral ovarian cystectomy for endometriosis, and a total of 23 mature oocytes were vitrified. After surgery, her pathologic reports revealed a serous borderline tumor and endometrioma. Fifteen months after her second surgery of laparoscopic right salpingo-oophorectomy and left ovarian cystectomy owing to recurrence, she had been married by then, and three of the frozen oocytes were thawed for intracytoplasmic sperm injection. These oocytes were cryopreserved for 2.5 years. All three were fertilized, and two grade-A cleavage-stage embryos were transferred.A singleton pregnancy was achieved, resulting in the delivery of a healthy baby boy at 39.3 weeks of gestation. Oocyte cryopreservation is an effective method for fertility preservation prior to ovarian surgery when ovarian function decline is predictable.
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Background@#Female infertility is a crucial problem with significant implications for individuals and society. In this study, we explore risk factors for infertility in Korean women. @*Methods@#A total of 986 female patients who visited six major infertility clinics in Korea were recruited from April to December 2014. Fertile age-matched controls were selected from two nationwide survey study participants. Conditional logistic regression after age-matching was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of each risk factor for infertility. @*Results@#Women with a body mass index (BMI) < 18.5 kg/m2 had 1.35 times higher odds of infertility (OR, 1.35; 95% CI, 1.03–1.77), while those with a BMI ≥ 25.0 kg/m2 had even higher odds (OR, 2.06; 95% CI, 1.61–2.64) compared to women with a normal BMI (18.5 kg/m2 ≤ BMI < 25 kg/m 2 ). Ever-smokers exhibited 4.94 times higher odds of infertility compared to never-smokers (95% CI, 3.45–8.85). Concerning alcohol consumption, women who consumed ≥ 7 glasses at a time showed 3.13 times significantly higher odds of infertility than those who consumed ≤ 4 glasses at a time (95% CI, 1.79–5.48). Lastly, women with thyroid disease demonstrated 1.44 times higher odds of infertility compared to women without thyroid disease (95% CI, 1.00–2.08). @*Conclusion@#Female infertility in Korea was associated with underweight, obesity, smoking, alcohol consumption, and thyroid disease.
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Fertility preservation is a major concern in young patients diagnosed with breast cancer and planning to receive multimodality treatment, including gonadotoxic chemotherapy with or without age-related decline through long-term endocrine therapy. Most breast cancer patients undergo multimodality treatments; many short-term and long-term side effects arise during these therapies. One of the most detrimental side effects is reduced fertility due to gonadotoxic treatments with resultant psychosocial stress. Cryopreservation of oocytes, embryos, and ovarian tissue are currently available fertility preservation methods for these patients. As an adjunct to these methods, in vitro maturation or gonadotropinreleasing hormone agonist could also be considered. It is also essential to communicate well with patients in the decision-making process on fertility preservation. It is essential to refer patients diagnosed with breast cancer on time to fertility specialists for individualized treatment, which may lead to desirable outcomes. To do so, a multimodal team-based approach and in-depth discussion on the treatment of breast cancer and fertility preservation is crucial. This review aims to summarize infertility risk related to currently available breast cancer treatment, options for fertility preservation and its details, barriers to oncofertility counseling, and psychosocial issues.
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Purpose@#Fertility preservation (FP) is an important issue for young survivors of breast cancer. Although international guidelines recommend pre-treatment fertility counseling for women with breast cancer, there is no standardized protocol or referral system for FP in South Korea. There are also barriers to discussing FP that make patient-centered decision making difficult. This study aimed to develop a shared decision making program for FP and compare the rates of FP procedures between the usual care and shared decision making groups. We hypothesized that multidisciplinary shared decision making for FP would increase the rate of FP procedures and patient satisfaction. @*Methods@#The multidisciplinary shared decision making for FP in young women with breast cancer (MYBC) is a multicenter, clustered, stepped-wedge, randomized trial. A total of 1100patients with breast cancer, aged 19–40 years, from nine hospitals in South Korea, will be enrolled. They will be randomized at the institutional level and assigned to usual care and shared decision making groups. Four institutions, each of which can recruit more than 200 patients, will each become a cluster, whereas five institutions, each of which can recruit more than 50 patients, will become one cluster, for a total of five clusters. The shared decision making groups will receive multidisciplinary programs for FP developed by the investigator. The primary outcome is the rate of FP procedures; secondary outcomes include fertility results, satisfaction, and quality of life. Outcomes will be measured at enrollment, treatment initiation, and the 1-, 3-, and 5-year follow-ups after starting breast cancer treatment.Discussion: A multidisciplinary shared decision making program for FP is expected to increase fertility rates and satisfaction among young patients with breast cancer. This study will provide the evidence to implement a multidisciplinary system for patients with breast cancer.
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As the number of cancer survivors has increased with advancements in cancer treatment, fertility preservation has become a treatment goal. Ovarian tissue cryopreservation (OTC) and transplantation (OTT) has made great progress over the past few decades. It has become the treatment of choice for fertility preservation in adolescents or patients in urgent need of chemotherapy. However, it is considered to be experimental compared with oocyte or embryo cryopreservation in some countries. Nevertheless, OTC and OTT is regarded as the more ideal method for fertility preservation in that it can also restore hormonal functions.Current Concepts: Currently, over 200 live births have been reported worldwide after OTC and OTT, proving the excellence of the technology. However, before its application in clinical settings, some challenges, including cryoinjury, ischemic injury, and cancer cell reimplantation, should be overcome. For cryoinjury, studies are underway on protocol improvement with the addition of agents such as antifreeze protein during cryopreservation. For ischemic injury, various agents have been studied to promote angiogenesis or revascularization. Furthermore, studies are underway on artificial ovary or xenotransplantation for fertility preservation in an effort to avoid cancer cell metastasis.Discussion and Conclusion: OTC and OTT is a clinically applicable option for fertility preservation. To set OTC and OTT as an established method for fertility preservation, further research is necessary to overcome the current challenges.
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Objective@#The aim of this study was to assess the correlation of oocyte number with serum anti-Müllerian hormone (AMH) levels measured by two automated methods (Access or Elecsys) in fresh stimulated in vitro fertilization (IVF) cycles. @*Methods@#In this retrospective study at a university hospital, data were collected from 243 fresh stimulated IVF cycles performed from August 2016 to December 2020. The serum AMH level was measured by Access in 120 cycles and by Elecsys in 123 cycles. The cut-off of serum AMH for prediction of poor responders (three or fewer oocytes) or high responders (15 or more oocytes) was calculated by the receiver operating characteristic curve analysis. @*Results@#For the two automated methods, the following equations were derived: total oocyte number=2.378+1.418×(Access-AMH) (r=0.645, p<0.001) and total oocyte number=2.417+2.163×(Elecsys-AMH) (r=0.686, p<0.001). The following combined equation could be derived: (Access-AMH)=0.028+1.525×(Elecsys-AMH). To predict poor responders, the cut-off of Access-AMH was 1.215 ng/mL (area under the curve [AUC], 0.807; 95% confidence interval [CI], 0.730–0.884; p<0.001), and the cut-off of Elecsys-AMH was 1.095 ng/mL (AUC, 0.848; 95% CI, 0.773–0.923; p<0.001). To predict high responders, the cut-off of Access-AMH was 3.450 ng/mL (AUC, 0.922; 95% CI, 0.862–0.981; p<0.001), and the cut-off of Elecsys-AMH was 2.500 ng/mL (AUC, 0.884; 95% CI, 0.778–0.991; p<0.001). @*Conclusion@#Both automated methods for serum AMH measurement showed a good correlation with oocyte number and good performance for predicting poor and high responders in fresh stimulated IVF cycles. The Access method usually yielded higher measured serum AMH levels than the Elecsys method.
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Objective@#This prospective consecutive study investigated the variation in sperm DNA fragmentation (SDF) in multiple semen samples from patients with cancer. @*Methods@#Eighty-one patients with various cancers underwent multiple semen collections on 3 consecutive days for sperm cryopreservation prior to cancer treatment. A commercial Halosperm kit was used to measure SDF. Within- and between-subject coefficients of variation were estimated via random-effects analysis of variance to assess the consistency of semen parameters and SDF. Intraclass correlation coefficients (ICCs) were calculated to assess the magnitude of the between-subject component of variance relative to the total variance. @*Results@#The volume of semen in the day-2 and day-3 samples was significantly lower compared with the day-1 sample. Most parameters showed high ICC values, suggesting that within-subject fluctuations were small relative to the between-subject variability. The highest ICC values were identified for the SDF (ICC, 0.68; 95% confidence interval [CI], 0.45–0.84) and semen volume (ICC, 0.67; 95% CI, 0.45–0.84). @*Conclusion@#Our findings showed that repeated ejaculates from patients with cancer had stable SDF levels.
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Purpose@#In women, menopause manifests with a variety of symptoms related to sex-hormone deficiency. Supplementing steroid hormones with pharmacological drugs has been widely practiced. However, considering the possible complications associated with artificial hormone therapy, studies have been conducted to find an alternative to pharmacological hormone replacement therapy. Accordingly, this study aimed to evaluate the efficacy of tissue-based hormone replacement therapy (tHRT) for treating post-menopausal signs and symptoms. @*Materials and Methods@#CD-1 mice were ovariectomized, and the ovaries were cryopreserved. Following artificial induction of post-menopausal osteoporosis, cryopreserved ovaries were subcutaneously autografted, and indexes related to bone health were monitored for 12 weeks. Bone mineral density (BMD), bone mineral contents (BMC), total bone volume (BV), and body fat mass were measured by dual energy X-ray absorptiometry. Uterine atrophy was assessed histologically, and bone microstructures were imaged by micro-computed tomography analysis. @*Results@#Regardless of the number of grafted ovaries, the BMC, BMD, and BV values of mice that underwent ovary transplantation were better than those that did not undergo transplantation. The uteruses in these mice were thicker and heavier after auto-transplantation. Furthermore, the bone microstructure recovered after tHRT. @*Conclusion@#Recovery of menopause-related bone loss and uterine atrophy was achieved through tHRT. Ovarian tissue cryopreservation and transplantation may be applicable not only in patients wanting to preserve fertility but also in sex hormone-deficient post-menopausal women.
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Humanity is in the midst of the coronavirus disease 2019 (COVID-19) pandemic, and vaccines—including mRNA vaccines—have been developed at an unprecedented speed. It is necessary to develop guidelines for vaccination for people undergoing treatment with assisted reproductive technology (ART) and for pregnancy-related situations based on the extant laboratory and clinical data. COVID-19 vaccines do not appear to adversely affect gametes, embryos, or implantation; therefore, active vaccination is recommended for women or men who are preparing for ART. The use of intravenous immunoglobulin G (IVIG) for the treatment of immune-related infertility is unlikely to impact the effectiveness of the vaccines, so COVID-19 vaccines can be administered around ART cycles in which IVIG is scheduled. Pregnant women have been proven to be at risk of severe maternal and neonatal complications from COVID-19. It does not appear that COVID-19 vaccines harm pregnant women or fetuses; instead, they have been observed to deliver antibodies against severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) to the fetus. Accordingly, it is recommended that pregnant women receive COVID-19 vaccination. There is no rationale for adverse effects, or clinical cases of adverse reactions, in mothers or neonates after COVID-19 vaccination in lactating women. Instead, antibodies to SARS-CoV-2 can be delivered through breast milk. Therefore, breastfeeding mothers should consider vaccination. In summary, active administration of COVID-19 vaccines will help ensure the safe implementation of ART, pregnancy, and breastfeeding.
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The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective contraceptive method that has several noncontraceptive benefits. It has been used in various gynecological conditions, such as heavy menstrual bleeding, dysmenorrhea, and endometrial hyperplasia. During the perimenopausal period, hormonal fluctuations occur, and there is a high tendency for the development of several benign gynecologic diseases. Therefore, the use of LNG-IUS in perimenopausal women might be more beneficial than in women belonging to other age groups. Moreover, the insertion of LNG-IUS during the perimenopausal period could confer endometrial protection during estrogen replacement therapy. In this review, we discuss the use of LNG-IUS in perimenopausal women.
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The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective contraceptive method that has several noncontraceptive benefits. It has been used in various gynecological conditions, such as heavy menstrual bleeding, dysmenorrhea, and endometrial hyperplasia. During the perimenopausal period, hormonal fluctuations occur, and there is a high tendency for the development of several benign gynecologic diseases. Therefore, the use of LNG-IUS in perimenopausal women might be more beneficial than in women belonging to other age groups. Moreover, the insertion of LNG-IUS during the perimenopausal period could confer endometrial protection during estrogen replacement therapy. In this review, we discuss the use of LNG-IUS in perimenopausal women.
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Objective@#This study aimed to investigate sperm motility and its changes after preparation as predictors of pregnancy in intrauterine insemination (IUI) cycles. @*Methods@#In total, 297 IUI cycles from January 2012 to December 2017 at a single tertiary hospital were retrospectively analyzed. Patient and cycle characteristics, and sperm motility characteristics before and after processing were compared according to clinical pregnancy or live birth as outcomes. @*Results@#The overall clinical pregnancy rate per cycle was 14.5% (43/297) and the live birth rate was 10.4% (30/289). Patient and cycle characteristics were similar between pregnant and non-pregnant groups. Sperm motility after preparation and the total motile sperm count before and after processing were comparable in terms of pregnancy outcomes. Pre-preparation sperm motility was significantly higher in groups with clinical pregnancy and live birth than in cycles not resulting in pregnancy (71.4%±10.9% vs. 67.2%±11.7%, p=0.020 and 71.6%±12.6% vs. 67.3%±11.7%, p=0.030, respectively). The change in sperm motility after processing was significantly fewer in the non-pregnant cycles, both when the comparison was conducted by subtraction (post-pre) and division (post/pre). These relationships remained significant after adjusting for the female partner’s age, anti-Müllerian hormone level, and number of pre-ovulatory follicles. According to a receiver operating characteristic curve analysis, an initial sperm motility of ≥72.5% was the optimal threshold value for predicting live birth after IUI. @*Conclusions@#Initial sperm motility, rather than the motility of processed sperm or the degree of change after preparation, predicted live birth after IUI procedures.
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Uterine leiomyoma is a very common gynecological tumor in the reproductive years. Recent studies have shown that surgical treatment of uterine leiomyoma using robotic-assisted laparoscopic myomectomy (RALM) is associated with significantly fewer complications, lower estimated blood loss, fewer conversions, and less bleeding than conventional laparoscopic myomectomy. This study reports the case of a giant uterine leiomyoma treated using RALM. A 50-year-old woman was referred to our outpatient clinic with progressive abdominal distension. Ultrasonography and magnetic resonance imaging were performed and showed a markedly enlarged uterus containing a 28-cm uterine myoma. RALM confirmed the 28-cm subserosal myoma on the posterior wall of the uterus. The myoma was enucleated, and the myometrial and serosal defect was repaired with a continuous suture using barbed suture materials. The entire myoma was removed using an electric morcellator. The operation lasted for 190 minutes. The total weight of the removed myoma was 3,262 g, and uterine leiomyoma was pathologically diagnosed. There were no postoperative complications. Although the treatment of huge myomas using RALM is controversial and technically demanding, we successfully performed RALM in a patient with a large myoma. This case confirms the efficiency, reliability, and safety of a robotic-assisted laparoscopic approach for removing a huge myoma. In a well-selected case, RALM can be performed by experienced surgeons regardless of the size of fibroids.
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Objective@#This study aimed to investigate sperm motility and its changes after preparation as predictors of pregnancy in intrauterine insemination (IUI) cycles. @*Methods@#In total, 297 IUI cycles from January 2012 to December 2017 at a single tertiary hospital were retrospectively analyzed. Patient and cycle characteristics, and sperm motility characteristics before and after processing were compared according to clinical pregnancy or live birth as outcomes. @*Results@#The overall clinical pregnancy rate per cycle was 14.5% (43/297) and the live birth rate was 10.4% (30/289). Patient and cycle characteristics were similar between pregnant and non-pregnant groups. Sperm motility after preparation and the total motile sperm count before and after processing were comparable in terms of pregnancy outcomes. Pre-preparation sperm motility was significantly higher in groups with clinical pregnancy and live birth than in cycles not resulting in pregnancy (71.4%±10.9% vs. 67.2%±11.7%, p=0.020 and 71.6%±12.6% vs. 67.3%±11.7%, p=0.030, respectively). The change in sperm motility after processing was significantly fewer in the non-pregnant cycles, both when the comparison was conducted by subtraction (post-pre) and division (post/pre). These relationships remained significant after adjusting for the female partner’s age, anti-Müllerian hormone level, and number of pre-ovulatory follicles. According to a receiver operating characteristic curve analysis, an initial sperm motility of ≥72.5% was the optimal threshold value for predicting live birth after IUI. @*Conclusions@#Initial sperm motility, rather than the motility of processed sperm or the degree of change after preparation, predicted live birth after IUI procedures.
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Uterine leiomyoma is a very common gynecological tumor in the reproductive years. Recent studies have shown that surgical treatment of uterine leiomyoma using robotic-assisted laparoscopic myomectomy (RALM) is associated with significantly fewer complications, lower estimated blood loss, fewer conversions, and less bleeding than conventional laparoscopic myomectomy. This study reports the case of a giant uterine leiomyoma treated using RALM. A 50-year-old woman was referred to our outpatient clinic with progressive abdominal distension. Ultrasonography and magnetic resonance imaging were performed and showed a markedly enlarged uterus containing a 28-cm uterine myoma. RALM confirmed the 28-cm subserosal myoma on the posterior wall of the uterus. The myoma was enucleated, and the myometrial and serosal defect was repaired with a continuous suture using barbed suture materials. The entire myoma was removed using an electric morcellator. The operation lasted for 190 minutes. The total weight of the removed myoma was 3,262 g, and uterine leiomyoma was pathologically diagnosed. There were no postoperative complications. Although the treatment of huge myomas using RALM is controversial and technically demanding, we successfully performed RALM in a patient with a large myoma. This case confirms the efficiency, reliability, and safety of a robotic-assisted laparoscopic approach for removing a huge myoma. In a well-selected case, RALM can be performed by experienced surgeons regardless of the size of fibroids.
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Radical trachelectomy is a fertility-preserving alternative to radical hysterectomy in carefully selected young women with early-stage cervical cancer. However, in cases with subsequent severe cervical stenosis, assisted reproductive techniques can be difficult. This is a case report of a 34-year-old patient who underwent robot-assisted radical trachelectomy and cerclage for early-stage (IB2) adenosquamous carcinoma. Three months after surgery, the patient underwent ovarian stimulation using a gonadotropin-releasing hormone antagonist protocol. As it was impossible to perform transcervical embryo transfer due to the almost complete absence of the cervical opening, transmyometrial embryo transfer under ultrasound guidance was performed. This resulted in a successful singleton pregnancy. This is the first case of successful pregnancy conceived by in vitro fertilization with transmyometrial embryo transfer in a patient who had previously undergone robot-assisted radical trachelectomy.
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Radical trachelectomy is a fertility-preserving alternative to radical hysterectomy in carefully selected young women with early-stage cervical cancer. However, in cases with subsequent severe cervical stenosis, assisted reproductive techniques can be difficult. This is a case report of a 34-year-old patient who underwent robot-assisted radical trachelectomy and cerclage for early-stage (IB2) adenosquamous carcinoma. Three months after surgery, the patient underwent ovarian stimulation using a gonadotropin-releasing hormone antagonist protocol. As it was impossible to perform transcervical embryo transfer due to the almost complete absence of the cervical opening, transmyometrial embryo transfer under ultrasound guidance was performed. This resulted in a successful singleton pregnancy. This is the first case of successful pregnancy conceived by in vitro fertilization with transmyometrial embryo transfer in a patient who had previously undergone robot-assisted radical trachelectomy.
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Endometriosis is a common inflammatory disease in women of reproductive age and is one of the major causes of infertility. Endometriosis causes a sustained reduction of ovarian reserve through both physical mechanisms and inflammatory reactions, which result in the production of reactive oxygen species and tissue fibrosis. The severity of endometriosis is related to ovarian reserve. With regard to infertility treatment, medical therapy as a neoadjuvant or adjuvant to surgical therapy has no definite beneficial effect. Surgical treatment of endometriosis can lead to ovarian injury during the resection of endometriotic tissue, which leads to the deterioration of ovarian reserve. To overcome this disadvantage, a multistep technique has been proposed to minimize the reduction of ovarian reserve. When considering surgical treatment of endometriosis in patients experiencing infertility, it should be kept in mind that ovarian reserve can be reduced both due to endometriosis itself and by the process of removing endometriosis. In cases of mild- to moderate-stage endometriosis, intrauterine insemination with ovarian stimulation after surgical treatment may increase the likelihood of pregnancy. In cases of severe endometriosis, the characteristics of the patient should be considered in a multidisciplinary manner to determine the prioritization of treatment modalities, including surgical treatment and assisted reproduction methods such as in vitro fertilization. The risk of cancer, complications after pregnancy, and infection during oocyte retrieval should also be considered when making treatment decisions.
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Objective@#The purpose of this study was to determine the effect of vaginal progesterone for luteal phase support (LPS) on the clinical pregnancy rate (CPR) in natural frozen embryo transfer (FET) cycles via a meta-analysis. @*Methods@#We performed a meta-analysis of randomized controlled trials (RCTs) and retrospective studies that met our selection criteria. Four online databases (PubMed, Embase, Medline, and the Cochrane Library) were searched between January 2017 and May 2017. Studies were selected according to predefined inclusion criteria and meta-analyzed using R software version 2.14.2. The main outcome measure was CPR. @*Results@#A total of 18 studies were reviewed and assessed for eligibility. One RCT (n=435) and three retrospective studies (n=3,033) met the selection criteria. In a meta-analysis of the selected studies, we found no significant difference in the CPR (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.60–1.55) between the vaginal progesterone and control groups. An analysis of the two retrospective cohort studies that reported the live birth rate (LBR) following FET showed a significantly higher LBR in the vaginal progesterone group (OR, 1.72; 95% CI, 1.21–2.46). A subgroup meta-analysis of FET conducted 5 days after injection of human chorionic gonadotropin showed no significant differences between the two groups with regard to the CPR (OR, 1.18; 95% CI, 0.90–1.55) or miscarriage rate (OR, 0.73; 95% CI, 0.36–1.47). @*Conclusion@#The results of this meta-analysis of the currently available literature suggest that LPS with vaginal progesterone in natural FET cycles does not improve the CPR.