Clomiphene citrate (CC) is most commonly used as a first-line treatment of infertility. However, a disturbance of endometrial growth by the adverse effects of the CC has been recognized. Since a thin endometrium is recognized as a critical factor of implantation failure, preventing CC-induced thinning of the endometrium is important. This study was undertaken to investigate whether the modified CC treatments are useful to prevent a thin endometrium in patients undergoing CC treatments.
Methods
This study is a prospective, randomized controlled study. The study was performed at the Saiseikai Shimonoseki General Hospital during a 4-month period (May 2012 to September 2012). Sixty-six infertile women who had a thin endometrium (< 8 mm) during the standard CC treatment (50 mg/day on days 5-9 of the menstrual cycle) were enrolled. The patients were randomly divided into three groups: 22 patients were given 25 mg/day CC on days 5-9 (half-dose group), 22 patients were given 50 mg/day CC on days 1-5 (early administration group) and 22 patients received a standard CC treatment again (control group). Endometrial thickness at the induction of ovulation was assessed by ultrasonography. The primary endpoint of this study was an endometrial thickness.
Results
Half dose administration and early administration improved the endometrial thickness (≥ 8 mm) in 14 patients (70%) and in 19 patients (90%) respectively, while only 3 patients (15%) improved in endometrial thickness in the control group. The mean endometrial thickness was also significantly higher in the half dose group (8.6 ± 1.5 mm) and early administration group (9.4 ± 1.5 mm) compared to the control group (6.7 ± 1.8 mm). No side effect was observed in this study.
Conclusions
The modified treatment with a half-dose or early administration of CC significantly increased endometrial thickness in patients with a history of thin endometrium caused by the standard CC regimen. The modified CC treatments in this study can be beneficial for patients with a thin endometrium as a result of standard CC treatment.
PMID 24369731 24369731 DOI 10.1186/1757-2215-6-94 10.1186/1757-2215-6-94 Takasaki et al. 2013, Takasaki 2013
Cite this article
Takasaki, A., Tamura, H., Taketani, T., Shimamura, K., Morioka, H., & Sugino, N. (2013). A pilot study to prevent a thin endometrium in patients undergoing clomiphene citrate treatment.. Journal of ovarian research, 6(1), 94. https://doi.org/10.1186/1757-2215-6-94
Takasaki A, Tamura H, Taketani T, Shimamura K, Morioka H, Sugino N. A pilot study to prevent a thin endometrium in patients undergoing clomiphene citrate treatment.. Journal of ovarian research. 2013;6(1):94. doi:10.1186/1757-2215-6-94
Ovarian rejuvenation is an innovative procedure intended to restore ovarian fertility and development during the climacteric and has been used to enhance fertility in women with premature ovarian insufficiency (POI). This retrospective study was conducted to determine the effects of an intraovarian platelet-rich plasma (PRP) injection on ovarian stimulation outcomes in women referred to an in vitro fertilisation centre. Methods- Population: This was a retrospective observational study, and the inclusion criteria included women of reproductive age with at least one ovary with a history of infertility, hormonal abnormalities, an absence of a menstrual cycle, and premature ovarian failure. During the patient's first consultation, a detailed reproductive history was recorded, a pelvic scan for ovarian size was conducted, and hormonal analysis for follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), estradiol (E2), and luteinizing hormone (LH) was conducted. In the study, 469 women with a history of infertility, hormonal abnormalities, an absence of a menstrual cycle, and premature ovarian failure had hormonal levels recorded up to four months after treatment, and these were included in the study. The volume of peripheral blood required to prepare 6-8 mL of PRP for administration was 40-60 mL. The initial concentration of platelets in the peripheral blood sample was about 25000/µL, whereas the prepared PRP had a concentration of 900.000/µL. A volume of approximately 2-4 mL per ovary, depending on the ovarian volume, was used for the intraovarian injection. PRP intervention had significant effects on FSH concentration at the α = 0.05 level. Statistically significant increases in normal values of FSH and E2were observed for months three and four after the PRP intervention for all age groups. The results of our observational study revealed that a PRP intraovarian injection is associated with improved ovarian tissue and function. Future randomised clinical trials are needed to shed light on the use of PRP in ovarian rejuvenation before offering it routinely in clinical practice.
This study was designed to investigate if whole dimension subcortical ovarian administration of platelet-rich plasma with gonadotropin, in proximity to most ovarian follicles, is effective in restoring ovarian functions in women during early menopause. Platelet-rich plasma, prepared from 40 mL of autologous peripheral blood using the buffy coat method, was injected into extended subcortical area of bilateral ovaries along with recombinant follicle-stimulating hormone (rFSH) (Gonal-F 300IU) under laparoscopic guidance. The posttreatment ovarian folliculogenesis and serum levels of FSH, luteinizing hormone (LH), and estradiol were followed up for 6 months at weekly to monthly intervals. IVF was carried out in women resuming ovulatory functions. Twelve early menopausal women with mean age of 44.42 ± 2.84 were enrolled. After treatment, 11 women resumed their menstrual period in 37.1 ± 23.5 days. Their average serum FSH was 70.47 ± 20.92 and 26.22 ± 17.55 IU/L, luteinizing hormone was 34.81 ± 11.86 and 14.3 ± 12.8 IU/L, before and after treatment, respectively. The mid-cycle E2 was 251.1 ± 143.8 pg/mL. Ten oocyte retrievals were carried out among six participants, four of them received controlled ovarian stimulation and another two using natural ovulation cycles. Thirteen mature eggs were retrieved which were then ICSI fertilized to obtain 10 normally fertilized 2PN oocytes. Two participants had cleavage stage embryos transferred of which one achieved clinical pregnancy. Whole dimension subcortical ovarian administration of platelet-rich plasma with gonadotropin was shown to restore ovarian functions, at least temporarily, and could increase the probability of pregnancy using autologous oocytes in women with early menopause.
Sharma S et al., 2018·J Hum Reprod Sci·
Open Access
Gonadotropin stimulation is used as the second line of treatment in patients with thin endometrium following clomiphene citrate (CC) administration, which is associated with higher cost, multiple births, and ovarian hyperstimulation syndrome. Tamoxifen (TMX), a selective estrogen receptor modulator, acts as an agonist on the endometrium. The objective of the present study was to compare the efficacy of low-dose CC, TMX, and gonadotropins in women with thin endometrium (<7 mm) following Clomiphene in intrauterine insemination (IUI) cycles. SETTINGS AND A prospective observational study between December 2011 and June 2013 was carried out in a tertiary infertility center. Women (n = 502) undergoing IUI with endometrium <7 mm after 100 mg CC were included in the study and divided into three treatment groups. Women in Group A (n = 182, cycles = 364) received clomiphene (50 mg/day from day 3 to 7), Group B (n = 179, cycles = 342) received TMX (40 mg/day from day 3 to 7), and Group C (n = 141, cycles = 226) received continuous urine-derived follicle-stimulating hormone 75-150 IU from day 3 onward until human chorionic gonadotropin injection. Endometrial thickness (ET), pregnancy rate, and live birth rate were considered as main outcome measures. Multiple comparisons using one-way ANOVA and Schiff's test were performed. Pregnancy and live birth rate were significantly higher (P < 0.004) in TMX and gonadotropin groups compared to clomiphene. A number of follicles in the TMX group were found to be lower (P < 0.001) compared to other two groups. In polycystic ovary syndrome patients, ovulation induction with TMX resulted in inadequate response in more than half of the cycles. TMX can improve ET and live birth rate in patients with thin endometrium after clomiphene.
To study the effects of clomiphene citrate (CC) on the endometrium by ultrasound and to reveal the echogenic difference between the control cycle and the CC cycle. Retrospective study of patients before and during a CC treatment. Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan. PATIENT(S): Seventy-nine infertile women who had a spontaneous ovulation and a normal luteal function. INTERVENTION(S): Patients received 50 mg/d CC between days 5 and 9 of the menstrual cycle. MAIN OUTCOME MEASURE(S): Endometrial thickness, echogenic pattern of the endometrium, serum E2 content, and E2 and P receptor contents in the endometrium. RESULT(S): Endometrial thickness was significantly thinner during the CC cycle (7.6 +/- 1.4 mm, mean +/- SD, n = 79) than during the control cycle (8.5 +/- 1.7 mm, n = 79) on late proliferative days, but there was no significant difference on midsecretory days (10.8 +/- 2.2 mm during the CC cycle, n = 79; 11.2 +/- 2.2 mm during the control cycle, n = 79). The echogenic patterns, however, were different between the two cycles on midsecretory days. Moreover, the incidence in which patients showed a grade 3 endometrium on midsecretory days was significantly higher during the conceived CC cycle compared with the not-conceived CC cycle. Serum E2 levels were significantly higher, but E2 receptor contents in the endometrium were significantly lower during the CC cycle (67 +/- 46 fmol/mg, n = 13) compared with the control cycle (123 +/- 89 fmol/mg, n = 15) on late proliferative days. CONCLUSION(S): Clomiphene citrate affected the echogenic pattern of the endometrium, and most of the endometrium showed a grade 3 pattern on midsecretory days during the conceived CC cycle. Under the CC treatment, the comfortable endometrium for embryos might be different from the control cycle.