Methods Of Ovulation Induction Research Articles

A Preliminary Report of A Low-Dose Step-Up Regimen of Recombinant Human FSH for Young Women Undergoing Ovulation Induction with IUI.

The aim of this study was to evaluate the efficacy and safety of a recombinant human follicle stimulating hormone (r-FSH) low-dose step-up regimen for controlled ovarian hyperstimulation in patients undergoing ovulation induction (OI) with intrauterine insemination (IUI). The study was conducted in the Department of Obstetrics and Gynecology, Far Eastern Memorial Hospital, New Taipei, Taiwan. In this prospective, observational study, consecutive infertile women (20-35 years) with regular menstrual cycles and a normal baseline FSH level were prospectively enrolled between January 2010 and September 2010. A starting dose of 112.5 IU/day r-FSH was administered on day 3 and increased by 37.5 IU/day every 2 days until a follicle ≥11 mm in diameter was present. Recombinant human chorionic gonadotropin (r-hCG) was administered when a follicle ≥18 mm was noted. Monifollicular development was defined as only one follicle with a diameter ≥16 mm. Clinical pregnancy was defined as a pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs. A total of 29 women and 30 cycles were included. The mean daily dose of r-FSH to achieve a follicle of ≥11 mm in diameter was 131.3 ± 23.6 IU and the mean total dose was 1030.0 ± 383.2 IU. Approximately 41% of the cycles were monofollicular. Clinical pregnancy was observed in 9 (30.0%) cycles, and a fetal heart beat was observed in 7 (23.3%). There were no multiple pregnancies. Mild ovarian hyperstimulation syndrome, which was resolved with conservative management, was observed in 3 (10.0%) cycles. This r-FSH low-dose step-up regimen seems to be a feasible and practical method for OI in younger infertile women undergoing IUI.

The use of aromatase inhibitors for ovulation induction.

Approximately 15% of the infertile population faces an ovulatory disorder; most of them classified as WHO class two anovulation [polycystic ovarian syndrome (PCOS) prototype]. Worldwide, this translates into millions of patients and emphasizes the need of a simple, effective and well tolerated method of ovulation induction. In this review, we will revisit letrozole use in the subset of WHO class two ovulatory problems and evaluate the contribution of the last year's literature to its practice. In a multicentre, randomized controlled trial comparing letrozole with clomiphene in 750 PCOS patients having regular intercourse, live birth rates were significantly higher for the letrozole group [rate ratio 1.44, 95% confidence interval (95% CI) 1.10-1.87]. In a meta-analysis summarizing clinical trials testing aromatase inhibitors used alone or with other medical therapies for ovulation induction in PCOS patients, live birth rates were again significantly higher when letrozole was compared with clomiphene citrate [odds ratio (OR) 1.64, 95% CI 1.32-2.04]. A retrospective analysis of children born to infertile women assessed the congenital malformation rate after exposure to letrozole in comparison to clomiphene citrate and to natural conceptions. No significant differences in malformation rates were detected between the groups (2.9, 2.5 and 3.9%, respectively). High-level evidence supports letrozole as the first drug of choice for ovulation induction in the PCOS population. The increasing use of letrozole with pregnancy follow-up provides additional reassurance for foetal safety.

Aromatase inhibitors for subfertile women with polycystic ovary syndrome: summary of a Cochrane review

Polycystic ovary syndrome (PCOS) is a common cause of anovulatory subfertility. We evaluated the effectiveness and safety of aromatase inhibitors compared with other methods of ovulation induction in women with anovulatory PCOS.

Improvement of ovulation induction by additive injection of 17,20β-Dihydroxy-4-pregnen-3-one after human chorionic gonadotropin administration in a pelagic egg spawning marine teleost, nibe croakerNibea mitsukurii(Jordan & Snyder)

This study aimed to develop the consistent ovulation induction method in a pelagic egg spawning marine teleost, nibe croaker Nibea mitsukurii. Attempts to induce oocyte maturation and ovulation in nibe croaker using human chorionic gonadotropin (hCG; 0.5 IU g−1) resulted in the normal progression of oocyte maturation and hydration, but a failure to induce ovulation in many individuals. This ovulation disorder was similarly observed even when the dose of hCG was increased 10 times (5 IU g−1) or decreased to one tenth (0.05 IU g−1), indicating that it cannot be completely overcome solely by hCG administration. However, this ovulation disorder could be completely overcome by subsequent administration of 17,20β-dihydroxy-4-pregnen-3-one (DHP) at the appropriate dose (0.5 μg g−1) and time (20 h after hCG administration). An increase in the number of individuals that ovulated due to DHP administration led to an increase in individuals producing larvae, resulting in an approximately threefold increase in the estimated number of larvae produced compared with the group of fish administered hCG alone. Thus, this ovulation induction method using DHP administration after hCG was demonstrated to overcome the ovulation disorder in nibe croaker and could be applicable to commercially important species with similar ovulation problems.

Pulsatile GnRH therapy is an effective strategy for ovulation induction in women with hypothalamic amenorrhea and underlying polycystic ovary syndrome

The clinical entity of polycystic ovarian syndrome (PCOS) coexisting with underlying hypothalamic amenorrhea (HA) has been formally described recently. We have previously reported in a pilot study (Dubourdieu et al, 2012), that pulsatile GnRH therapy was an effective and safe method of ovulation induction in this specific subgroup of infertile women, in comparison with gonadotropins treatment. The aim of this study was to confirm our preliminary results in a larger cohort of HA/PCOS women.

Progesterone luteal support after ovulation induction and intrauterine insemination: a systematic review and meta-analysis

To evaluate the effect of luteal phase P support after ovulation induction IUI. A systematic review and meta-analysis. Not applicable. Undergoing ovulation induction IUI. Any form of exogenous P in ovulation induction IUI cycles. Clinical pregnancy and live birth. Five trials were identified that met inclusion criteria and comprised 1,298 patients undergoing 1,938 cycles. Clinical pregnancy (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.15-1.98) and live birth (OR 2.11, 95% CI 1.21-3.67) were more likely in P-supplemented patients. These findings persisted in analyses evaluating per IUI cycle, per patient, and first cycle only data. In subgroup analysis, patients receiving gonadotropins for ovulation induction had the most increase in clinical pregnancy with P support (OR 1.77, 95% CI 1.20-2.6). Conversely, patients receiving clomiphene citrate (CC) for ovulation induction showed no difference in clinical pregnancy with P support (OR 0.89, 95% CI 0.47-1.67). Progesterone luteal phase support may be of benefit to patients undergoing ovulation induction with gonadotropins in IUI cycles. Progesterone support did not benefit patients undergoing ovulation induction with CC, suggesting a potential difference in endogenous luteal phase function depending on the method of ovulation induction.

Three decades after Gjönnaess’s laparoscopic ovarian drilling for treatment of PCOS; what do we know? An evidence-based approach

The introduction of laparoscopic ovarian drilling (LOD) by Gjönnaess in 1984 as a substitute for ovarian wedge resection created opportunities for extensive research given its worldwide application for ovulation induction in women with polycystic ovary syndrome (PCOS). To critically evaluate and summarize the current body of literature regarding the role of LOD for the management of PCOS entailing its different preoperative, operative and postoperative aspects. In addition, long-term efficacy, cost-effectiveness, patient preference and health-related quality of life issues will be evaluated together with other available alternatives of ovulation induction treatments. A PubMed search was conducted looking for the different trials, reviews and various guidelines relating to the role of LOD in the management of PCOS. LOD whether unilateral or bilateral is a beneficial second-line treatment in infertile women with clomiphene citrate (CC)-resistant PCOS. It is as effective as gonadotrophin treatment but without the risk of multiple pregnancy or ovarian hyperstimulation and does not require intensive monitoring. Increased responsiveness of the ovary to CC especially in patients who remain anovulatory following LOD is another advantage. Recent evidence suggests that relatively novel oral methods of ovulation induction, e.g. CC plus metformin, CC plus tamoxifen, rosiglitazone plus CC and aromatase inhibitors represent a successful alternative to LOD in CC-resistant PCOS. Meanwhile current evidence does not support LOD as a first-line approach in PCOS-related anovulation or before IVF. LOD is currently recommended as a successful and economical second-line treatment for ovulation induction in women with CC-resistant PCOS.

Prospective, randomized comparison between pulsatile GnRH therapy and combined gonadotropin (FSH + LH) treatment for ovulation induction in women with hypothalamic amenorrhea and underlying polycystic ovary syndrome

To compare the efficacy of pulsatile GnRH therapy versus combined gonadotropins for ovulation induction in women with both hypothalamic amenorrhoea and polycystic ovarian syndrome (HA/PCOS) according to their current hypothalamic status. This single-centre, prospective, randomized study was conducted in the Nantes University Hospital, France. Thirty consecutive patients were treated for ovulation induction with either pulsatile GnRH therapy or combined gonadotropins (rFSH+rLH). Frequency of adequate ovarian response (mono- or bi-follicular) and clinical pregnancy rate were then compared between both groups. Ovarian response was similar in both groups with comparable frequency of adequate ovarian response (73% vs 60%), but the clinical pregnancy rate was significantly higher in the pulsatile GnRH therapy group than in the combined gonadotropin group (46% vs 0%). HA/PCOS is a specific subgroup of infertile women. Pulsatile GnRH therapy is an effective and safe method of ovulation induction that can be used successfully in these patients.

Abstract P2-11-02: Perception and practice of reproductive specialists towards fertility preservation of young breast cancer patients

Abstract Background: The potential for infertility caused by treatment is one of the important quality-of-life issues in young breast cancer (YBC) patients. Insufficient communication and partnership between oncologists and reproductive specialists has been identified as a major barrier to meeting their needs. However, the perception of reproductive specialists towards fertility preservation (FP) of YBC has not been evaluated. Objective: To investigate the perception and needs of reproductive specialists towards FP of YBC patients. Methods: A cross-sectional survey was developed and sent to 423 certified reproductive specialists registered to the Japan Society for Reproductive Medicine to self-evaluate their perceptions and practices regarding FP in YBC patients. Results: Two hundred reproductive specialists (47%) responded to the survey. 99% responded that reproductive specialists should be engaged in FP of YBC patients. 46% responded that cancer treatment is more important than childbirth even if the patient was recurrence-free five years after primary treatment. 83% responded that they would like to treat YBC patients. Respondents affiliated with private clinics were more likely to accept both fertilized egg and unfertilized egg preservation than those affiliated with academic or general hospitals (p < 0.01). 58% responded that ovulation induction methods should be modified in YBC patients. The choice of ovulation induction methods varied both in non-cancer women and YBC patients, however, the frequency of the use of letrozole was significantly higher (p < 0.01) and that of LHRH-agonist short protocol was significantly less (p < 0.05) in the management of breast cancer patients than in the practice of non-cancer women. 70% of the reproductive specialists responded that they were anxious in treating YBC patients. Concerns for greater or unknown risk of disease recurrence (66%), insufficient knowledge about breast cancer (47%), and lack of patient's spouse/partner (24%) were identified as major barriers in supporting FP for YBC patients. Conclusion Reproductive specialists recognize the needs of FP in YBC patients and are willing to participate and support care for YBC. Affiliation of reproductive specialists was related to positive attitude towards to egg preservation. Various concerns regarding FP among reproductive specialists indicate the need for evidence that supports the safety of FP for YBC patients and guidelines that facilitate the practice and communication of oncologists and reproductive specialists. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-02.

Is Metformin Indicated as Primary Ovulation Induction Agent in Women with PCOS? A Systematic Review and Meta-Analysis

Background: A recent meta-analysis has proven that metformin (M) is highly effective for ovulation induction in the clomiphene citrate (CC)-resistant patient. There is uncertainty whether M should be introduced as a primary ovulation induction agent in polycystic ovarian syndrome (PCOS). Methods: We conducted a systematic review and meta-analysis to establish if M is better when given alone or in combination with CC (CC+M) when compared with CC alone. This systematic review studied live birth delivery rate as the primary outcome. Results: We identified 14 prospective trials. Analysis of these results showed a reduction in the live birth rate in the group of patients treated only with M when compared with CC alone (OR = 0.48, 95% CI 0.31–0.73, p = 0.0006). An increase in ovulation (OR = 1.6, 95% CI 1.2–2.1, p = 0.0009) and pregnancy rate (OR = 1.3, 95% CI 1.0–1.6, p = 0.05) with CC+M when compared with CC alone was reported, but no difference was found when live birth rate was analyzed (OR = 1.1, 95% CI 0.8–1.5, p = 0.61). Conclusion: CC alone is superior to M alone regarding live birth rate and ovulation. The combination (CC+M) is superior to CC alone as a primary method for ovulation induction and to achieve pregnancy in PCOS. However, when addressing live birth rate, no statistically significant difference could be demonstrated. Because of the side effects profile and contraindications of M, we believe M should not be indicated as a primary ovulation induction agent in women with PCOS.

Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study

Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the hypothesis that pregnancy rate (PR) and live birth rates (LBR) are higher after OI with low-dose FSH than with CC as first-line treatment. Infertile women (<40 years old) with PCOS-related anovulation, without prior OI treatment, attending 10 centres in Europe/South America were randomized to OI with either CC (50-150 mg/day for 5 days) or FSH (starting dose 50 IU) for up to three treatment cycles. The primary outcome was clinical PR. Patients (n = 302) were randomized to OI with FSH (n = 132 women; 288 cycles) or CC (n = 123; 310 cycles). Per protocol analysis revealed that reproductive outcome was superior after OI with FSH than with CC with respect to PR per first cycle [30 versus 14.6%, respectively, 95% confidence interval (CI) 5.3-25.8, P = 0.003], PR per woman, (58 versus 44% of women, 95% CI 1.5-25.8, P = 0.03), LBR per woman (52 versus 39%, 95% CI 0.4-24.6, P = 0.04), cumulative PR (52.1 versus 41.2%, P = 0.021) and cumulative LBR (47.4 versus 36.9%, P = 0.031), within three cycles of OI. Pregnancies and live births are achieved more effectively and faster after OI with low-dose FSH than with CC. This result has to be balanced by convenience and cost in favour of CC. FSH may be an appropriate first-line treatment for some women with PCOS and anovulatory infertility, particularly older patients.

Ovulating induction methods in rabbit does: The pituitary and ovarian responses

The aim of this study was to compare the pituitary and ovarian responses in rabbit does subjected to different methods of ovulation induction. Forty-eight receptive females were randomly distributed into six groups (N = 8) and were inseminated with standard glass catheters. Buserelin intramuscular (BM) does were inseminated using a pool of fresh heterospermic semen and an intramuscular injection of 1 μg of buserelin acetate to induce ovulation. Buserelin intravaginal (BV) does were inseminated in a similar way, but ovulation was induced with the GnRH analogue (10 μg of buserelin acetate) combined with 0.5 mL of semen extender. The raw semen (R) and saline groups (S) were inseminated with undiluted semen or saline, respectively, without any inducer of ovulation. Another group (A) received lumbar anaesthesia (1.5 mL of 2% lidocaine), and only the empty catheter was introduced into the vagina. The AR does were treated the same way as group A but were inseminated with raw semen instead of an empty catheter. Blood samples were collected to determine the LH concentrations before and after AI (30, 60, 90, and 120 minutes). Ovulation, pregnancy, and conception rates were determined after euthanasia on day 14 post AI. Ovulating does had higher mean LH concentrations than nonovulating does (197.9 vs. 45.9 ng/mL; P < 0.05). The ovulation rates of buserelin intramuscular and intravaginal does were 100%, and the pregnancy rates were 87.5% and 100%, respectively. Rabbit does in groups A and AR did not ovulate and had similar mean plasma LH concentrations after 60 minutes compared with the S group (49.4 and 49.2 ng/mL vs. 41.6 ng/mL, respectively), which reached ovulation and pregnancy rates of 37.5%. Does inseminated only with raw semen had an ovulation rate of 75% and a pregnancy rate of 62.5%; they also demonstrated higher plasma LH concentrations than does of the S, A, and AR groups. In conclusion, ovulation in rabbit does can be induced by exogenous GnRH administration (im and intravaginal). The high plasma LH concentration and ovulation rate in the R group with respect to the S and A groups could weakly indicate the presence of some molecules in the seminal plasma that could act on or be absorbed by vaginal mucosa. Sensory stimulation and “seminal factors” probably exert a synergy on the ovulation response as demonstrated by the comparison of LH release and the ovulation response in the R, S, RA, and A groups.

Incomplete and inconsistent reporting of maternal and fetal outcomes in infertility treatment trials

Pregnancy outcomes and adverse outcomes in infertility trials are reported to varying extents; for example, 35% of clinical trials reported no information on pregnancy loss, only 43% reported adverse events during the preconception treatment period, and only 7% reported any serious adverse events. Incomplete reporting limits the value of these studies in counseling patients on the risk-benefit ratio of treatment to themselves and their infants.

Live birth prediction in polycystic ovary syndrome

Anovulatory infertility is common in polycystic ovary syndrome (PCOS). Clinicians who provide first-line treatment have to decide how best to induce ovulation with the desired outcome of live birth, a decision often complicated by the phenotypic heterogeneity of PCOS. Could a new live birth prediction model of different ovulation induction methods developed from basic clinical parameters help select infertility treatments?

Predictors of Pregnancy in Women with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. The selection of first-line therapies for ovulation induction is empiric. The aim of the study was to develop a clinically useful predictive model of live birth with varying ovulation induction methods. We built four prognostic models from a large multicenter randomized controlled infertility trial of 626 women with PCOS performed at academic health centers in the United States to predict success of ovulation, conception, pregnancy, and live birth, evaluating the influence of patients' baseline characteristics. Ovulation was induced with clomiphene, metformin, or the combination of both for up to six cycles or conception. The primary outcome of the trial was the rate of live births. Baseline free androgen index, baseline proinsulin level, interaction of treatment arm with body mass index, and duration of attempting conception were significant predictors in all four models. History of a prior loss predicted ovulation and conception, but not pregnancy or live birth. A modified Ferriman Gallwey hirsutism score of less than 8 was predictive of conception, pregnancy, and live birth (although it did not predict ovulation success). Age was a divergent predictor based on outcome; age greater than 34 predicted ovulation, whereas age less than 35 was a predictive factor for a successful pregnancy and live birth. Smoking history had no predictive value. A live birth prediction chart developed from basic clinical parameters (body mass index, age, hirsutism score, and duration of attempting conception) may help physicians counsel and select infertility treatments for women with PCOS.

New Methods for Induction of Ovulation

New Methods for Induction of Ovulation

Randomized controlled trial comparing laparoscopic ovarian diathermy with clomiphene citrate as a first-line method of ovulation induction in women with polycystic ovary syndrome

Laparoscopic ovarian diathermy (LOD) is currently accepted as a successful second-line treatment for ovulation induction (OI) in clomiphene citrate (CC)-resistant women with polycystic ovary syndrome (PCOS). The aim of this study was to test the hypothesis that LOD may be superior to CC as a first-line treatment. The study included 72 anovulatory women with PCOS who were randomized to LOD (n = 36) or CC (n = 36). Women who remained anovulatory after LOD were offered CC. Similarly, women receiving CC who failed to ovulate or conceive were offered LOD. Pregnancy rates were compared between the two groups using chi(2) and odds ratio with 95% confidence interval (OR, 95% CI). After randomization, six women conceived before starting treatment and another patient postponed treatment. The remaining 65 women received the treatment (33 underwent LOD and 32 received CC). After the primary treatment, more pregnancies (44%) occurred in women receiving CC than in those undergoing LOD (27%), although the difference did not reach statistical significance [P = 0.13, OR 2.1 (0.7 - 5.8)]. After adding the second treatment, the pregnancy rate was still higher, but to a less extent, in the CC group [63% versus 52%, P = 0.2, OR 1.6 (0.6 - 4.2)]. LOD is not superior to CC as a first-line method of OI in women with PCOS. The trial is registered with ClinicalTrials.gov with an identifier number NCT00220545.

Performing two inseminations rather than one in intrauterine insemination cycles may not improve outcome

OBJECTIVE: To determine whether performing one or two Intra-uterine inseminations (IUI) per ovulation induction cycle affect pregnancy rate.DESIGN: Retrospective chart review of all IUI cycles performed at a University Infertility clinic in 2007.MATERIALS AND METHODS: Charts of infertile couples undergoing IUI were identified and abstracted data included demographics, duration and cause of infertility, previous infertility treatment and outcome, menstrual and relevant gynecologic history, and previous pelvic surgery. Semen analysis and IUI specimen parameters were recorded. The status of the endometrial cavity and tubal patency was documented. Ovulation induction method and monitoring, if any, was also recorded. Day 3 FSH, antral follicular count, and clomiphene challenge test, when performed, were recorded. In cycles with one insemination, IUI was performed 1 to 1.5 days from LH surge or administration of hCG. In cycles with 2 inseminations, IUI was performed on the 2 consecutive days following LH surge or hCG administration.RESULTS: During the study period 123 patients completed 271 IUI cycles, with 2 inseminations per cycle performed in 140 cycles and one insemination in 131 cycles. There were 27 pregnancies with pregnancy rate (PR) of 10% per cycle and 22% per patient. Women younger than 30 yr significantly had higher PR per cycle than those older than 30yr (21.3% vs. 7.6%, p=0.004).The per cycle PR was significantly higher when the total motile sperm count was more than 5 million in the washed insemination sample (11.8% vs. 2%, p=0.037). The PR in the double insemination cycles was not significantly different from the PR in the single insemination cycles (9.3% vs. 10.7%, p= 0.7). In a logistic regression model controlling for covariates, there was no correlation between number of inseminations per cycle and PR. This model, however, showed a significant correlation between PR and total motile sperm count in the washed insemination sample (OR 1.02, p=0.003).CONCLUSIONS: Performing a second insemination during an IUI cycle does not seem to add any benefit to one insemination. PR seems to be more affected by the woman's age and the total number of motile sperms in the washed insemination specimen. OBJECTIVE: To determine whether performing one or two Intra-uterine inseminations (IUI) per ovulation induction cycle affect pregnancy rate. DESIGN: Retrospective chart review of all IUI cycles performed at a University Infertility clinic in 2007. MATERIALS AND METHODS: Charts of infertile couples undergoing IUI were identified and abstracted data included demographics, duration and cause of infertility, previous infertility treatment and outcome, menstrual and relevant gynecologic history, and previous pelvic surgery. Semen analysis and IUI specimen parameters were recorded. The status of the endometrial cavity and tubal patency was documented. Ovulation induction method and monitoring, if any, was also recorded. Day 3 FSH, antral follicular count, and clomiphene challenge test, when performed, were recorded. In cycles with one insemination, IUI was performed 1 to 1.5 days from LH surge or administration of hCG. In cycles with 2 inseminations, IUI was performed on the 2 consecutive days following LH surge or hCG administration. RESULTS: During the study period 123 patients completed 271 IUI cycles, with 2 inseminations per cycle performed in 140 cycles and one insemination in 131 cycles. There were 27 pregnancies with pregnancy rate (PR) of 10% per cycle and 22% per patient. Women younger than 30 yr significantly had higher PR per cycle than those older than 30yr (21.3% vs. 7.6%, p=0.004).The per cycle PR was significantly higher when the total motile sperm count was more than 5 million in the washed insemination sample (11.8% vs. 2%, p=0.037). The PR in the double insemination cycles was not significantly different from the PR in the single insemination cycles (9.3% vs. 10.7%, p= 0.7). In a logistic regression model controlling for covariates, there was no correlation between number of inseminations per cycle and PR. This model, however, showed a significant correlation between PR and total motile sperm count in the washed insemination sample (OR 1.02, p=0.003). CONCLUSIONS: Performing a second insemination during an IUI cycle does not seem to add any benefit to one insemination. PR seems to be more affected by the woman's age and the total number of motile sperms in the washed insemination specimen.

Use of letrozole in assisted reproduction: a systematic review and meta-analysis

BACKGROUNDLetrozole is the third-generation aromatase inhibitor (AI) most widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen production; the consequent hypoestrogenic state increases GnRH release and pituitary follicle-stimulating hormone (FSH) synthesis.METHODSA systematic search of the literature was performed for both prospective and retrospective studies. Meta-analyses of randomized clinical trials (RCTs) were performed for three comparisons: letrozole versus clomiphene citrate (CC), letrozole + FSH versus FSH in intrauterine insemination (IUI) and letrozole + FSH versus FSH in IVF. In the absence of RCTs, non-randomized studies were pooled.RESULTSNine studies were included in the meta-analysis. Four RCTs compared the overall effect of letrozole with CC in patients with polycystic ovary syndrome. The pooled result was not significant for ovulatory cycles (OR = 1.17; 95% CI 0.66–2.09), or for pregnancy rate per cycle (OR = 1.47; 95% CI 0.73–2.96) or for pregnancy rate per patient (OR = 1.37; 95% CI 0.70–2.71). In three retrospective studies which compared L + FSH with FSH in ovarian stimulation for IUI, the pooled OR was 1.15 (95% CI 0.78−1.71). A final meta-analysis included one RCT and one cohort study that compared letrozole + gonadotrophin versus gonadotrophin alone: the pooled pregnancy rate per patient was not significantly different (OR = 1.40; 95% CI 0.67–2.91).CONCLUSIONSLetrozole is as effective as other methods of ovulation induction. Further randomized-controlled studies are warranted to define more clearly the efficacy and safety of letrozole in human reproduction.

Induction of estrus in pubertal miniature gilts

Genetic engineering of miniature pigs has facilitated the development of numerous biomedical applications, such as xenotransplantation and animal models for human diseases. Manipulation of the estrus is one of the essential techniques for the generation of transgenic offspring. The purpose of the present study was to establish a useful method for induction of the estrus in miniature gilts. A total of 38 pubertal miniature gilts derived from 4 different strains were treated with exogenous gonadotropins. Estrus and ovulatory response were examined after treatment with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) as 200 IU PMSG and 100 IU hCG, 300 IU PMSG and 150 IU hCG, or 1500 IU PMSG only, followed by 100, 150 or 750 IU hCG 72 h later, respectively. The optimal protocol was determined to be the combination treatment of 200 IU PMSG and 100 IU hCG followed by 100 IU hCG. The administration of 200 IU PMSG and 100 IU hCG was effective in inducing estrus regardless of the strain, although there was a strain difference in the ovulatory response. These results indicate that treatment with a low-dose combination of PMSG and hCG provides one of the simplest methods for induction of estrus and ovulation in pubertal miniature pigs.