Usefulness of Newly Devised Clomiphene Citrate Administration Method Compared with the Conventional Method in Ovulation and Pregnancy

Objective: Since not all women wish to conceive a child through aggressive treatment, we investigated the usefulness of modified repeated intracyclic clomiphene citrate (CC) therapy (repeated CC therapy) as a newly devised administration method. Methods: We evaluated the effects of CC administration on menstrual cycle length and retrospectively compared ovulation and pregnancy in 220 women who received CC at our hospital. Patients in the conventional method group received 50 mg per day for five days, starting on the fifth day of menstruation (withdrawal bleeding). Groups with and without menstrual cycle shortening after conventional CC administration were compared. The repeated CC therapy group was also compared with the non-shortened group. Repeated CC therapy was administered for the first five days as in the conventional method, and a second five-day repeat treatment was administered after an interval of five to seven days. Pregnancy rates, including indirect pregnancies, were evaluated by three different methods. Results: Ovulation and pregnancy rates were significantly better in the shortened group than in the non-shortened group (P < 0.001 and P = 0.010, respectively). Even in the non-shortened group, ovulation and pregnancy rates including indirect pregnancies were significantly improved when ovulation was observed with repeated CC therapy (P < 0.001 and P = 0.022, respectively). Conclusions: For patients whose menstrual cycle was not improved or shortened, repeated CC therapy as the newly devised CC administration method is useful as the next step after the conventional CC administration method.

Ovarian pregnancy rupture following ovulation induction and intrauterine insemination:A case report

BACKGROUND Ovarian pregnancy after assisted reproductive technology treatment has rarely been reported;ovarian pregnancy following intrauterine insemination(IUI)is even rarer,and only nine cases have previously been reported.CASE SUMMARY We report a case of ovarian pregnancy rupture after ovulation induction and IUI.The patient presented with bilateral lower abdominal pain and was referred to the emergency department.Ultrasound examination revealed ovarian pregnancy and intraperitoneal bleeding.Laparoscopy revealed an ovarian pregnancy with hemoperitoneum,which was subsequently removed.Pelvic adhesions were detected intraoperatively,which were treated immediately.The patient spontaneously conceived an intrauterine pregnancy 3 mo later,which was ongoing at the time of writing this study.CONCLUSION Close attention should be paid to any history of pelvic inflammatory disease before commencing IUI treatment,and patients with such a history should be closely followed up after IUI.Early measurement of serumβ-human chorionic gonadotropin levels and ultrasonic examination are essential for timely diagnosis of ovarian pregnancy after ovulation induction and IUI to avoid more serious complications.

Chinese traditional medicine for induction of ovulation

This is a review paper of some effective recipes of Chinese traditional medicine usedin ovulation induction and treatment of gynecological diseases. Some clinical results bygynecologists using Chinese traditional medicine in combination with western medicineand results from research on traditional medicine with modern technology are presented.A list of frequently used traditional medicine for ovulation induction are selected from the famous Compendium of Materica Medica(本草纲目)by Li Shi-zhen(李时珍).

Ovulation induction in the gynecological cancer patient

Malignancy is a serious disease that can lead to serious morbidity and mortality. However, the survival rates for women with cancers have increased significantly during the past decades, reflecting improved diagnosis and treatment. With the increased survival in young women with cancer, more attention is being paid to preservation of fertility, which is potentially jeopardized by chemotherapy and radiation therapy, aiming to limit the devastating sequelae of this serious illness by providing these young women with a hope for motherhood. In vitro fertilization with oocyte or embryo cryopreservation has emerged as an astounding method to preserve fertility. It entails induction of ovulation to produce oocytes, the number and quality of which are imperative factors predicting the potential efficacy of the fertility preservation procedure. The aim of this review is to discuss ovarian stimulation for fertility preservation in women with gynecological cancer.

Management strategy of infertility in polycystic ovary syndrome

Polycystic ovary syndrome(PCOS)is the most common endocrine and metabolic disease in women of reproductive age.PCOS is characterized by ovulatory disruption,which can lead to infertility.Patients with PCOS are also more likely to have poor pregnancy outcomes.For obese women,lifestyle interventions are recommended first,which have general health benefits.For women who have difficulty changing their lifestyle,drugs for the treatment of obesity or bariatric surgery could be considered.Clomiphene citrate is the first-line medication after weight loss that has been utilized in the past.Letrozole is supplanting clomiphene as the best option for ovulation induction for now,particularly in patients with PCOS.Metformin can improve ovulation and pregnancy rates;however,it has minimal effects in terms of raising live birth rates.Second-line therapies include gonadotropins and laparoscopic ovary drilling.In vitro fertilization can be utilized as a third-line treatment for patients with PCOS who have failed ovulation induction therapy or have other infertility factors.In summary,to achieve fertility,patients with PCOS require standardized individualized therapy.

Ovarian hyperstimulation syndrome following the use of GnRH agonist trigger of final oocyte maturation and freeze-all strategy: A case report and review of the literature

Rationale:The current literature has a surprising controversy regarding the use of low-dose human chorionic gonadotropin(hCG)for luteal support as an explanation for the development of ovarian hyperstimulation syndrome,and this is because of the gap in the listing of the predisposing factors that put women at an increased risk of ovarian hyperstimulation syndrome.Patient concerns:A case of 25-year-old woman presented with abdominal pain,distention,dyspnea,and nausea with a 6.5 kg increase in weight from baseline.Ultrasonographic examination showed bilaterally enlarged multicystic ovaries after gonadotropin-releasing hormone(GnRH)agonist triggering and cycle segmentation with no hCG rescue administration.Diagnosis:Moderate/severe ovarian hyperstimulation syndrome.Interventions:The woman was admitted to the hospital for medical management of moderate/severe ovarian hyperstimulation syndrome,and pain management was advanced to patient-controlled anesthesia with the start of low molecular weight heparin.On day 2,albumin therapy followed by a furosemide chase was started due to an increase in abdominal girth.On day 1,Cabergoline was maintained,and on day 2 the GnRH antagonist Cetrorelix was started.Outcomes:The woman’s clinical condition improved,and a clinical pregnancy was eventually achieved during the first cryo-warmed blastocyst cycle.Lessons:Ovarian hyperstimulation syndrome can still happen even after the use of GnRH agonist and avoidance of hCG support.Segmentation of in vitro fertilization with complete avoidance of hCG for luteal support remains the best approach.

Heterochronic bilateral ectopic pregnancy after ovulation inductionHeterochronic bilateral ectopic pregnancy after ovulation induction

Ectopic pregnancy is identified with the widely-applied assisted reproductive technology （ART）. Bilateral ectopic pregnancy is a rare form of ectopic pregnancy which is difficult to be diagnosed at the pre-operation stage. In this paper, we presented an unusual case of heterochronic bilateral ectopic pregnancy after stimulated intrauterine insemination （IUI）, where there has been a delay of 22 d between the diagnoses of the two ectopic pregnancies. Literature was reviewed on the occurrence of bilateral ectopic pregnancy during the past four years in the MEDLINE database. We found 16 cases of bilateral ectopic pregnancy reported since 2008, and analyzed the characteristics of those cases of bilateral ectopic pregnancy. We emphasize that ovulation induction and other ARTs may increase the risk of bilateral ectopic pregnancy. Because of the difficulty in identification of bilateral ectopic pregnancy by ultraso- nography, the clinician should be aware that the treatment of one ectopic pregnancy does not preclude the occurrence of a second ectopic pregnancy in the same patient and should pay attention to the intra-operation inspection of both side fallopian tubes in any ectopic pregnancy case.

Therapeutic Effect Observation on Combined Acupuncture and Medication for Ovulation

Objective：To observe the curative effect of acupuncture plus medicine in treating ovulatory dysfunctional infertility.Method：All 36 cases with anovulatory infertility were randomly allocated into a control group （19 cases） and an observation group （17 cases）.The cases in the control group were treated with 50 mg of oral administration Clomiphene once a day for 5 d,and 50 menstrual cycles were observed.The cases in the observation group were treated with combined acupuncture and the same medication as those in the control group and 45 menstrual cycles were observed.During the treatment sessions,the follicular development,ovulation,thickness of the endometrium,cervical mucus and pelvic fluid were observed and recorded.Results：The cases in the observation group showed significantly higher ovulation and pregnancy rates,along with thickening of the endometrium.In addition,no luteinized unruptured follicle syndrome （LUFS） occurred in the observation group.Conclusion：Acupuncture coupled with oral administration Clomiphene can obtain higher ovulation and conception rates than oral Clomiphene alone.

Effects of the Interval between Ovulation Induction using Clomiphene Citrate and Frozen Embryo Transfer on Pregnancy Outcome

Objective:To explore the best timing for frozen embryo transfer(FET)after ovarian stimulation and egg retrieval using the clomiphene citrate(CC)+human menopausal gonadotropin(hMG)ovulation induction regimen through a retrospective analysis.Methods:Data of patients who underwent CC+hMG ovulation induction and FET from January 2014 to December 2019 were analyzed retrospectively.The patients were divided into three groups according to the interval from egg retrieval to FET:CC1(within 1 menstrual cycle),CC2(2 menstrual cycles),and CC3(≥3 menstrual cycles).Indicators such as hormone levels and pregnancy outcomes were recorded to explore the effect of different intervals on pregnancy outcome.Results:A total of 1,082 transfer cycles were included in this retrospective analysis.The implantation,clinical pregnancy,and live birth rates in the CC1 group were significantly lower than those in the CC2 and CC3 groups(P<0.05).The E2/P4 ratio on progesterone injection day(3 days before thawed embryo transfer)was lower in the CC1 group than in the other groups(P<0.05).After adjusting for all factors using multifactor regression analysis,the interval between egg retrieval and FET was found to be an independent predictor of the implantation,pregnancy,and live birth rates.Conclusion:An interval of more than one menstrual cycle between the day of egg retrieval after ovarian stimulation with the CC+hMG ovulation induction regimen and the day of FET can result in high implantation,clinical pregnancy,and live birth rates,which can lead to an improved pregnancy outcome.

Induction of Ovulation with Clomiphene Citrate Combined with Bromocriptine in Polycystic Ovary Syndrome Patients with Infertility: A Prospective, Randomized, and Controlled Clinical Trial

Background:To investigate the therapeutic effects of bromocriptine(BCT)combined with clomiphene citrate(CC)in the induction of ovulation in polycystic ovary syndrome(PCOS)patients with infertility.Methods:A prospective,randomized,and controlled clinical trial was performed on 100 PCOS patients with infertility.Patients were randomly divided into two groups(n=50),patients in control group were treated with 50 mg CC from day 3 to day 7 of the menstrual cycle,and those in observation group(CC+BCT)were given 50 mg of CC from day 3 to day 7 of the menstrual cycle along with 2.5 mg of BCT daily for the full cycle.Patients in both groups were treated for one cycle.Blood was extracted from patients on day 3 of the menstrual cycle,the day of human chorionic gonadotrophin(hCG)injection,and day 7 after hCG injection to measure serum levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),prolactin(PRL),estradiol(E_(2)),total testosterone(T)and progestin(P).Vaginal ultrasound was used to determine the thickness of endometrium and follicle size and count.Results:There was no significant difference in basal hormone levels between two groups.The success rate of ovulation induction in control group and observation group was 72.0%and 75.4%,respectively,no significant difference was found between two groups(P>0.05).The ongoing pregnancy rate(18.4%)in observation group was significantly higher than that in control group(8.0%).On the day of hCG injection,no significant differences in the levels of FSH,E_(2),and P were found between two groups,while LH was lower,and levels of PRL and T were significantly lower in observation group than those in control group(all P=0.00).On day 7 after hCG injection,no significant differences in the levels of E_(2) and P were found between two groups,while PRL level was significantly lower in observation group than that in control group,and the endometrial thickness in observation group(10.20±1.92 mm)was significantly higher than that in control group(9.22±1.88 mm)(P=0.01).Conclusions:Compared with the use of CC alone,BCT combined with CC can increase the success rate of ovulation induction-assisted pregnancy in PCOS patients,decrease the levels of PRL,LH,and T and increase the endometrial thickness in implantation window.Those data suggest that dopamine agonist BCT may reduce the pituitary hormone and androgen levels,reduce endometrial vascular resistance,and increase endometrial blood supply to improve the infertility outcomes of PCOS patients with infertility.

Therapeutic Efficacy Observation on Electroacupuncture for Ovulatory Dysfunctional Infertility

Objective：To observe the clinical effect of electroacupuncture for ovulatory dysfunctional infertility by ovulation stimulation.Methods：A total of 65 patients were randomly allocated into a treatment group （38 cases） and a control group （27 cases）.Acupuncture plus electric stimulation was employed in the treatment group,whereas oral Clomifene Citrate Tablets in the control group,50 mg per day.Results：After six months （2 sessions） of treatment,the cure rate in the treatment group was 76.3%,versus 48.1% in the control group,showing a significant difference between the two groups （P〈0.05）.Conclusion：Electroacupuncture can obtain better cure rate than oral Clomifene Citrate Tablets for infertility via ovulation stimulation.

An Impact of Suspected Peritubal Adhesions by Hysterosalpingography on Outcomes of Intrauterine Insemination

Objective To assess the fertility prospect of women with suspected peritubal adhesions diagnosed by hysterosalpingography （HSG） treated with intrauterine insemination （IUI）. Methods The study group consisted of 93 patients diagnosed as bilateral suspected peritubal adhesions by HSG, and 175 patients with no tubal pathology were classified as control group. A total of 496 cycles of lUI were finished in 268 infertile women. Results There were no differences in basic clinical parameters between the two groups. Cumulative pregnancy rates after two cycles of lUI were 19.4%for the study group, and 34.3%for the control. Cumulative pregnancy rate in the women with abnormal contrast media loculation was significantly lower than that in women of the control （7.4% vs 34.3%, P=0.037）. The cumulative pregnancy rates were similar between the women with abnormal tubal contour and the normal ones （36. 7% vs 34.3%, P=0.800）. Conclusion Suspected peritubal adhesions in HSG were worthy more attention, since the outcome of lUI in women with loculation of contrast material, combined with or without abnormal tubal contour resulted in a significantly lower pregnancy rate than the normal ones. IUI should be delayed before tubal patency was confirmed during these patients.

Circulating anti-Müllerian hormone as predictor of ovarian response to gonadotrophins in women with polycystic ovary syndrome

Objective To investigate the impact of high circulating anti-Müllerian hormone（AMH）on the outcome of ovulation induction using human menopausal gonadotropin（hM G）in women with polycystic ovary syndrome（PCOS）.Methods This prospective study included 63 anovulatory women with PCOS who underwent hM G ovarian stimulation. Serum AMH concentrations were compared between responders and non-responders. The receiver-operating characteristic（ROC）curve was used to evaluate the prognostic value of circulating AMH.Results hM G responders had a significantly lower serum AMH concentration compared with non-responders（8.43±2.18 μg/L vs 11.05±2.85 μg/L, P〈0.001）. In multivariate Logistic regression analysis, AMH was an independent predictor of ovulation induction by hM G in PCOS patients. ROC curve analysis showed AMH was a useful predictor of ovulation induction by hM G in PCOS patients, having 91.7% specificity and 66.7% sensitivity when the threshold AMH concentration was 10.12 μg/L.Conclusion Serum AMH can be used as an effective parameter to predict ovarian response to hM G treatment in PCOS patients.