Case series of a single centre's treatment of ovulatory infertility with clomiphene citrate and intrauterine insemination in 2002

The present paper reports a single department's retrospective case series of all clomiphene citrate (CC) combined with intrauterine insemination (IUI) treatment cycles for ovulatory infertility performed during 2002. Thirty-eight couples with unexplained, endometriosis, male or unilateral tubal factor infertility had undergone 71 cycles of CC and IUI. The clinical and ongoing cycle pregnancy rates were 20 and 17%, respectively. Seven percent of the clinical pregnancies were multiple pregnancies, with all multiple pregnancies being twin gestations. The current use of CC and IUI is an effective early treatment option in couples with ovulatory infertility presenting to our department.     

Effect of repeated administration of clomiphene citrate at two different times on the endometrium in patients undergoing intrauterine insemination

Background, Aims and Methods:  Clomiphene citrate (CC) has been widely used for induction of ovulation; however, despite the high rate of ovulation, the pregnancy rate is only 30%. The anti-estrogenic effect of CC on the endometrium is one explanation for this finding. It is well known that repeated administration of CC enhances its anti-estrogenic effect. To overcome this adverse affect, a number of techniques have been used. One technique is the early administration of CC, in an attempt to decrease the anti-estrogenic effects of CC on the endometrium. The aim of the present study was to retrospectively evaluate if repeated administration of CC at varying times may affect the endometrium during preovulatory period; pregnancy rates were compiled for patients with unexplained infertility undergoing intrauterine insemination (IUI). The patients were divided into four groups based on the number of repeat administrations and the time of CC administration.
Results:  The endometrial thickness at the day of human chorionic gonadotropin administration was greater in early administration within three consecutive CC cycles than the others.
Conclusion:  When the endometrium is thin during classical administration of CC, it is worth attempting the early administration of CC in the CC/IUI treatment for patients with unexplained infertility. However, this effect disappeared over the duration of the three consecutive CC cycles. (Reprod Med Biol 2004; 3 : 153–157)     

Minimal stimulation protocol for use with intrauterine insemination in the treatment of infertility

OBJECTIVE: To determine whether minimal stimulation with clomiphene and one injection of 150 IU of human menopausal gonadotrophin (hMG) provides pregnancy rates comparable with those in a conventional full hMG stimulation protocol for infertile patients undergoing intrauterine insemination (IUI). METHODS: A prospective study was carried out at the Infertility Clinic of a teaching institute and tertiary care referral center in Chandigarh, India. Two hundred couples with either unexplained infertility or ovulatory dysfunction cases who ovulated with clomiphene citrate (CC) but failed to conceive were offered ovarian stimulation with CC and hMG along with IUI for 420 cycles. Pregnancy rate, medication and monitoring cost were compared between minimal and conventional stimulation protocols. RESULTS: There was no difference in the couples of the two stimulation protocols regarding their age, duration and type of infertility as well as cause of infertility. Number of ampoules of hMG and monitoring costs were significantly higher in the full hMG stimulation cases whereas pregnancy rate was comparable in both protocols. CONCLUSION: Minimal stimulation appears to be an effective protocol in cases of unexplained infertility undergoing intrauterine insemination. Reduced cost and minimal monitoring is appealing to patients and the clinician.     

The effects of clomiphene citrate on normally ovulatory women

Objective: To investigate the efficacy of clomiphene citrate (CC) on normally ovulatory women who complained of infertility.

Design: A randomized study.

Setting: University Hospital.

Patient(s): Thirty-three normally ovulatory women with unexplained infertility.

Intervention(s): Eighteen women received CC at a 50-mg dosage. Fifteen women received no ovulation-induction drugs.

Main Outcome Measures: The pregnancy rate (PR) per patient, the PR per cycle, and the cumulative pregnancy rate.

Result(s): Seven patients in the CC group stopped taking CC, and observations were terminated because of antiestrogenic effects. The pregnancy rate (PR) per patient and the PR per cycle were significantly decreased (P < 0.005) in the CC group (4 of 18 [22.2%] and 4 of 66 [6.1%], respectively) than in the spontaneous group (11 of 15 [73.3%] and 11 of 52 [21.2%], respectively). Kaplan-Meier tests showed that the cumulative pregnancy rate in the CC group was significantly lower than in the spontaneous group (P <0.05). Five of seven patients who had stopped taking CC became pregnant in spontaneous cycles.

Conclusion(s): Administration of CC to normally ovulatory women is not efficacious in terms of increasing the pregnancy rate.     

A randomized double-blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory function in normal women

OBJECTIVE: To evaluate the ovarian follicular dynamics of cycle modification with the aromatase inhibitor letrozole compared with clomiphene citrate in normal ovulatory women. DESIGN: Randomized double-blind controlled trial. SETTING: Tertiary care hospital. PATIENT(S): Nineteen ovulatory female volunteers, ages 18-35 years. INTERVENTION(S): Subjects were monitored in one control cycle. Subjects then received either letrozole 2.5 mg daily or clomiphene citrate 50 mg daily on days 5-9 after menses. MAIN OUTCOME MEASURE(S): Number of mature follicles, endometrial thickness and endometrial pattern at ovulation, and follicular profiles of LH, FSH, and E(2). RESULT(S): The number of mature follicles at the LH surge in natural cycles was 1.0 with an exaggerated response seen for treatment both with clomiphene and letrozole. There was no difference in the endometrial thickness at midcycle during either the natural cycles or the medicated cycles. LH surges and spontaneous ovulation were documented in all natural and medicated cycles. When measured daily, follicular profiles of LH and FSH are similar between the groups in both the natural and medicated cycles. In the medicated cycles, clomiphene results in a significant increase in E(2) levels, while E(2) levels in letrozole-stimulated cycles appeared lower than in natural cycles. CONCLUSION(S): Transient inhibition of aromatase activity in the early follicular phase with the aromatase inhibitor letrozole results in stimulation of ovarian folliculogenesis similar to that seen with clomiphene citrate with no apparent adverse effect on endometrial thickness or pattern at midcycle.     

Effect of inseminated volume on intrauterine insemination

Purpose: Intrauterine insemination (IUI) is a method for the treatment of marital infertility involving the intrauterine or fallopian deposition of washed spermatozoa, depending on the amount of inseminated semen. In view of the divergent opinions about the inseminated volume, the objective of this study was to compare the two techniques (3.0 mL or 0.5 mL) in two groups of patients. Methods: We performed 164 cycles of ovulation induction followed by IUI. The patients were divided into two groups according to the technique used. Group low volume – 50 cycles and 0.5 mL of inseminated semen; Group high volume – 114 cycles and 3.0 mL of inseminated semen. The cycle was monitored on the basis of endometrial thickness and follicular development measured by transvaginal ultrasound. Human chorionic gonadotrophin (hCG) was administered in the presence of a follicle measuring 18 mm in mean diameter. The procedure was performed after sperm washing using a discontinuous PureSperm® gradient, 40 h later. Results: We obtained a similar clinical pregnancy rate for the two groups (14.0% for Group low volume and 15.7% for Group high volume). There was one abortion in each group. We detected no interference by any etiology of infertility or by the total motile recovered sperm with pregnancy rate. Conclusions: The results did not demonstrate superiority of one method over the other, with both therapeutic alternatives being satisfactory for the treatment of infertile couples.     

Timed intercourse after intrauterine insemination for treatment of infertility

Objective: To compare the pregnancy rates, between intrauterine insemination (IUI) followed by timed intercourse and IUI only for treatment of the infertile couples. Study design: A prospective study of two different protocols of intrauterine insemination in two hundred and one infertile couples with a normal spermiogram was carried out. Of these, 101 couples were treated with IUI alone and 100 couples had both IUI and timed intercourse within a 12-18 h period. The pregnancy rates were compared between groups. Results: The characteristics of the two groups were similar in terms of the mean age, as well as the duration and causes of infertility. The cycle characteristics following follicular stimulation were also similar between two groups. The pregnancy rate per cycle increased with increasing numbers of total motile sperm per insemination in the IUI alone group (P=0.045). Timed intercourse increased pregnancy rate in patients with lower motile sperm number (<40×10⁶) (27.7% versus 10.5%, P=0.023), but not in patients with higher sperm number (≥40×10⁶) (25.7% versus 22.7%, P=0.671). Conclusions: In IUI with low number of motile sperm inseminated, timed intercourse significantly increases the pregnancy rates over IUI alone in infertile couples with a normal sperminogram. This alternative treatment appears to be a practical, simple, and inexpensive addition that improves the pregnancy rate in patients receiving ovulation induction and intrauterine insemination program.     

Luteal phase clomiphene citrate for ovulation induction in women with polycystic ovary syndrome: a systematic review and meta-analysis

Objective: To assess the efficacy of late luteal phase clomiphene citrate (CC) administration relative to early follicular phase CC for ovulation induction for polycystic ovary syndrome (PCOS).

Study design: Review.

Materials and methods: A complete electronic databases including PubMed, Embase, The Cochrane Library, Web of Science, and CBM were searched for relevant randomized controlled trials (RCTs). The search was not restricted by language and publication time. Two reviewers selected trials and assessed trial quality by the Cochrane Handbook 5.1.0 independently.

Results: Four eligible RCT studies involving 708 women (934 cycles) were included. The results of the Meta-analysis: Late luteal phase group was associated with a number of higher total follicles (MD 1.82; 95% CI 0.86–2.78, p?p?p?=?0.26), ovulation rate (RR 0.99; 95% CI 0.86–1.14, p?=?0.87), and abortion rate (RR 1.12; 95% CI 0.38 to 3.29, p?=?0.84) between the two groups.

Conclusion: It appeared that late luteal phase CC for ovulation induction might be an effective method for ovulation induction in women with PCOS compared to conventional CC administration. Further intensive randomized-controlled studies should be warranted to define the efficacy of CC used in late luteal phase.     

人绝经期促性腺激素联合氯米芬或来曲唑用于多囊卵巢综合征患者促排卵疗效比较

的探讨人绝经期促性腺激素（HMG）＋氯米芬（CC）、HMG和来曲唑（LE）＋HMO对多囊卵巢综合征（PCOS）患者宫腔内供精人工授精的治疗效果。方法将2007年12月-2008年5月期间在我中心就诊的114例PCOS妇女的114个宫腔内人工授精（AID）周期分为3组：CC＋HMG周期组38个周期，HMG周期组38个周期，LE＋HMG周期组38个周期。分析比较3组的年龄、血清T水平、绒毛膜促性腺激素肌肉注射日（HCG日）平均卵泡直径（MFD）≥14mm的卵泡（成熟卵泡）个数、平均卵泡E2水平、子宫内膜厚度、HCG日单优势卵泡发育成熟百分率、HMG用量和周期妊娠率。结果CC＋HMG组、HMG组和LE＋HMG组患者年龄和血清T水平比较，差异无显著性（P〉0．05），CC＋HMG组HCG日成熟卵泡个数为（2．9±1．6）个，明显多于其他两组[HMG组为（1．6±1．0）个，LE＋HMG组为（1．9±1．2）个]，差异有显著性（P〈0．05），而内膜厚度较其他两组薄，差异有显著性（P〈0．05），HMG组与LE＋HMG组HCG日成熟卵泡个数和子宫内膜厚度比较，差异无显著性（P〉0．05）。3组HCG日单优势卵泡发育成熟百分率分别21．05％、78．95％和52．63％，差异有显著性（P〈0．05）。CC＋HMG组、HMG组和LE＋HMG组HMG用量分别为（4．89±1．59）支和（9．88±4．59）支、（9．68±4．67）支（75IU／支），CC＋HMG组与后两组比较，差异有显著性（P=0．00）。HMG组、LE＋HMG组HMG用量比较，差异无显著性（P〉0．05）。3组的周期妊娠率分别为36．84％、39．48％和31．57％，差异无显著性（P〉0．05）。结论HMG促排卵周期更易得到单优势卵泡发育成熟；CC＋HMG促排卵HMG用药量最少；CC＋HMG、HMG和LE＋HMG均可获得满意的周期妊娠率。     

Characteristics of baseline ovarian cysts in clomiphene citrate ovulation cycles

To evaluate the incidence and factors associated with ovarian cysts in infertile patients receiving clomiphene citrate (CC), we performed a retrospective cohort study involving 466 CC treatment cycles. Ovarian cysts are a common finding in patients presenting for CC, with approximately one in five patients having a baseline ovarian cyst >10 mm.     

Laparoscopy for the treatment of unexplained infertility

Aim:  To determine the best treatment for unexplained infertility.
Methods:  A retrospective study was used to examine Japanese women with unexplained infertility that had undergone laparoscopy. The main outcome measure of the study was the rate of pregnancy after laparoscopy.
Results:  One hundred and thirty-eight women diagnosed with unexplained infertility received laparoscopy and as a result 55 women had their diagnosis of unexplained infertility confirmed. There were no statistically significant differences between the women who became pregnant after laparoscopy in terms of duration of infertility, duration of treatment or age. The pregnancy rate of women with unexplained infertility was 56.4%, with 90% of these pregnancies achieved within the first 6 months. There were 64 women with minor endometriosis considered to be suffering from unexplained infertility before laparoscopy. The characteristics of the patients in the unexplained infertility group and in the minor endometriosis group were similar, but patients with minor endometriosis were found to have a lower pregnancy rate compared to those with unexplained infertility (35.9% vs 56.4%; P  = 0.02).
Conclusions:  The effective period after laparoscopy appears to be 6 months. Assisted reproductive technology should be considered after that time. Pregnancy rates were low in women with minor endometriosis compared with unexplained infertility. It is important to clarify the cause of infertility using laparoscopy. (Reprod Med Biol 2006; 5 : 59–64)