To report a unique fluoroscopically guided approach to treat severe intrauterine adhesions and cervical stenosis using balloon hysteroplasty.
Military-based fertility center.
A 33-year-old woman undergoing assisted reproductive technologies whose uterus could not be cannulated because of the development of intrauterine synechiae and cervical stenosis following a post-intrauterine insemination infection that was further complicated by a prominent lower uterine segment filling defect in the location of a prior cesarean delivery scar.
Fluoroscopic cannulation and balloon uterine dilation.
Main Outcome Measure
Resolution of synechiae by hysterosalpingogram and successful uterine cannulation.
A post-procedure hysterosalpingogram demonstrated a normalized uterine cavity with the exception of a persistent prominent lower uterine segment filling defect from a prior cesarean delivery. A frozen embryo transfer cycle was performed successfully.
Hysteroplasty, using standard interventional radiographic techniques, may provide an alternative treatment modality for patients with intrauterine adhesions and lower uterine defects from prior cesarean deliveries, in select cases. While treating intrauterine adhesions improves pregnancy outcome, the effect of lower uterine segment filling defects from cesarean deliveries on pregnancy outcome in assisted reproductive technology cycles warrants further investigation.
Asherman’s syndrome; synechiae; intrauterine adhesions; balloon dilation; cesarean section scar
A 34-year-old woman was referred to the in vitro fertilisation (IVF) clinic following failure to conceive after ovulation induction with antioestrogens and intrauterine insemination. She had a long history of hypothalamic amenorrhoea secondary to weight loss and stress and received hormone replacement to maintain her bone density. She also underwent radical trachelectomy and bilateral laparoscopic pelvic node dissection as fertility sparing surgery for cancer of the cervix stage 1B. She remained under our care for 4 years during which she had two successful IVF pregnancies with elective single embryo transfers on both occasions. She delivered preterm by caesarean section at 31 weeks and 35 weeks, respectively, for premature rupture of membranes with good outcomes. There was no evidence of local or distant recurrence of her early cervical cancer at 10-year follow-up at the combined gynaecology oncology clinic and she was discharged to primary care for follow-up.
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.
fallopian perfusion; infertility; intrauterine insemination; ovulation induction
Intrauterine insemination with or without controlled ovarian hyperstimulation is a viable treatment option for male factor, cervical factor and unexplained infertility.We enumerate our 10 year experience in performing intrauterine insemination at a government teaching hospital setup.
Retrospective observational study.
Nine hundred eighty nine couples were observed for 3104 treatment cycles.Male factor and anovulation were the two common causes of infertility in this cohort. Out of the 232 pregnancies that occurred during the study, 34.05% resulted in live birth. Highest cycle fecundity was seen in cases of idiopathic infertility (16%) followed by male factor infertility (15%). 91.8% conceptions occurred in the 1st cycles of intrauterine insemination.
In the resource deprived Indian scenario controlled ovarian hyperstimulation with intrauterine insemination is an effective, less invasive, feasible & financially acceptable modality for the treatment of sub-fertility.
intrauterine insemination; male factor; idiopathic infertility; ovarian; hyperstimulation
Purpose: The objective was to determine the optimal insemination technique in patients undergoing in vitro fertilization (IVF) after failed direct intraperitoneal insemination (DIPI) and the outcome of intracytoplasmic sperm injection (ICSI) in such cases.
Methods: In case–control studies, 53 couples with unexplained infertility who underwent IVF after four failed DIPI cycles were compared with 75 couples with tubal or endometriosis infertility as controls. Thirty couples with unexplained infertility after failing to conceive with DIPI and conventional IVF who underwent ICSI and 58 couples with male-factor infertility as controls also were compared. Fertilization cleavage, embryo quality, implantation, and pregnancy were compared after IVF and after ICSI.
Results: There was a significant difference in fertilization rates after IVF between cases of unexplained infertility after failing to conceive with DIPI (40.4%) and patients with tubal or endometriosis infertility (67.9%). There also was a significant difference in total fertilization failure rates between the two groups (30.4% and 3.9%, respectively). There was a slight but significant difference in numbers of fertilized oocytes after ICSI between patients with low fertilization rate undergoing IVF after failing to conceive DIPI (85.8%) and patients with male factor (90.4%). Total fertilization failure was not observed in these cases.
Conclusions: Couples with unexplained infertility after failing to conceive with DIPI show a failed fertilization or a low fertilization rate after IVF. However, they demonstrated a good chance of becoming pregnant after subsequent ICSI, even with statistically significant difference in fertilization rate as compared with male-factor cases.
intracytoplasmic sperm injection; unexplained infertility; in vitro fertilization; direct intraperitoneal insemination; failed fertilization
Infertility afflicts fifteen percent of couples who wish to conceive. Despite intensive evaluation of both male and female partners, the etiology may remain unknown leading to a diagnosis of unexplained infertility. For such couples, treatment often entails ovulation induction (OI) with fertility medications coupled with intrauterine insemination. Complications of this therapy include ovarian hyperstimulation syndrome and creation of multiple gestation pregnancies, which can be complicated by preterm labor and delivery, and the associated neonatal morbidity and expense of care for preterm infants. The Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) study is designed to assess whether OI in couples with unexplained infertility with an aromatase inhibitor produces mono-follicular development in most cycles, thereby reducing multiple gestations while maintaining a comparable pregnancy success rate to that achieved by OI with either gonadotropins or clomiphene citrate. These results will provide future guidance of therapy for couples with unexplained infertility, and if comparable pregnancy rates are achieved with a substantial reduction in multiple gestations, the public health benefit will be considerable.
Multiple gestation; ovulation induction; gonadotropins; aromatase inhibitor; unexplained infertility
Smooth atraumatic embryo transfer is paramount for the success of in-vitro fertilization (IVF). In difficult cases, cervical canal manipulation may be required.
To see if surgical correction of the cervical canal or cervical canal refashioning could improve ease of embryo transfer.
Private infertility and IVF hospital.
MATERIALS AND METHODS:
Patients: 11 women with failed 1-3 IVF cycles with history of extremely difficult embryo transfers (ETs) despite undergoing cervical dilatation in the cycle prior to IVF.
Operative hysteroscopy using Versapoint for refashioning of the cervical canal.
MAIN OUTCOME MEASURES:
Ease of ET in the subsequent IVF cycle. Secondary outcome measure was to assess reproductive outcome.
Easy and atraumatic ET in the IVF cycle after procedure in 100% patients. PR was 46.5%.
Use of Versapoint for refashioning the cervical canal can improve the quality of ET and PR.
Cervical stenosis; embryo transfer; hysteroscopy; in vitro fertilization; Versapoint
Objective: To demonstrate that folliculogenesis can be sustained with 200 IU human chorionic gonadotropins (hCG) after FSH-priming and result in pregnancy in women with estrogenic ovulatory dysfunction and risk factors for severe ovarian hyperstimulation syndrome (OHSS).
Design:Case report: Three women with infertility associated with estrogenic ovulatory dysfunction and hyperinsulinemia who appeared to be at high risk for severe OHSS during gonadotropin therapy.
Interventions: After 10 days of receiving either 150 IU hMG or recombinant FSH, patients were switched to 200 IU hCG/day alone for 2–3 days. 5,000 IU of hCG was then administered followed by either home intercourse, intrauterine insemination or transvaginal oocyte retrieval-embryo transfer.
Main Outcome Measures: Endovaginal ultrasound measurement of follicle number and size, serum estradiol levels, symptoms of ovarian hyperstimulation, pregnancy test, and evaluation of pregnancy by transvaginal ultrasound.
Results: After discontinuation of hMG or recombinant FSH, serum estradiol concentrations continued to rise, and follicles > 14 mm continued to grow during low-dose hCG administration. All women conceived without developing symptoms of OHSS. Pregnancy outcomes achieved include a term singleton delivery, a term twin delivery, and triplets delivered at 31 weeks gestation.
Conclusion: The use of low-dose hCG alone is sufficient for supporting the late stages of folliculogenesis in women with estrogenic ovulatory dysfunction. This ovulation induction regimen appears to support the follicular growth of larger follicles while decreasing the number of smaller preovulatory follicles, thereby reducing a known risk factor for OHSS. We report on the positive pregnancy outcomes in 3 women with estrogenic ovulatory dysfunction and clinically appeared to be at high risk for developing severe OHSS who safely underwent this protocol.
Gonadotropin therapy; infertility; ovarian hyperstimulation syndrome; polycystic ovarian syndrome; pregnancy
The objective of our study is to investigate the optimum number of stimulated intrauterine insemination (SIUI) or donor insemination (DI) cycles that can be offered to the couples prior to in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in a tertiary referral unit for assisted reproduction.
This is a retrospective analysis of 408 SIUI and 704 DI cycles performed in a tertiary referral unit for assisted reproduction. SIUI’s were performed by controlled ovarian hyperstimulation and ovulation induction followed by insemination 36 h later. DI’s were performed in natural or stimulated cycles after thawing frozen donor sperm. The main outcome measured was cumulative live birth rate (CLBR) per couple.
A maximum CLBR of 26.1% was achieved after the fourth cycle of SIUI. The CLBR of DI increased to 60.1% in the sixth cycle.
This study, in line with a number of other studies, is unable to demonstrate unequivocally whether increasing numbers of IUI or DI cycles are justified clinically or financially. There is a need for larger datasets from multiple centres along with rigorous randomised trials to compare treatment pathways. Until then, the resources spent on the provision of extra SIUI cycles may be better utilized by early referral to IVF.
Cumulative live birth; Donor insemination; In vitro fertilization; Stimulated insemination; Intracytoplasmic sperm injection
To evaluate the efficacy of in vitro fertilization (IVF) and intra-uterine insemination (IUI) in couples with unexplained and mild male factor infertility.
One hundred fifty couples were allocated to treatment with IVF and IUI, both following the same protocol (clomiphene citrate and follicle stimulating hormone (FSH) injection) depending upon their hormonal response. The mild male factor patients were included in the study because we observed that their rate of failed fertilization was not different from those in couples with unexplained infertility. They had ovulatory cycles confirmed by recent ovulatory mid luteal phase progesterone measurement and bilateral tubal patency, which was confirmed by laparoscopy or hysterosalpingography. Men with unexplained infertility had semen analysis with a sperm concentration ≥25×106/ml, motility (grdel + 2) ≥40% and normal forms ≥25%. Men with mild male factor infertility had semen analysis where only one of the above parameters was below the normal range.
Among the 150 couples, 75 were treated with IVF and 75 were treated with IUI. The mean age of women allocated to IVF was 32.9 years compared to 33.2 years for the IUI treatment group. Cycle day 2 basal plasma estradiol, LH and FSH concentrations were also not different (geometric means; Estradiol 244 and 245 pmol/1, LH 4.9 and 5.3 IU/1, FSH 7.5 and 7.7 IU/1 in the IVF and IUI treatment groups, respectively).
IUI is the first choice of treatment for unexplained and mild male factor infertility with a lower cost and the equal efficacy as IVF. Treatment delivered within the context of a specialized IVF center will be more efficient and safer because of the potential to salvage over-responding cycles by conversion to IVF.
unexplained infertility; male factor; IVF; IUI
Purpose:Our purpose was to compare ovarian performance and hormonal levels, after ovulation induction, in both normal ovulatory women undergoing intrauterine insemination (group 1) and World Health Organization (WHO) group II anovulatory infertile patients (group 2), using two different gonadotropin drugs.
Methods:Patients (n = 20 per group) were treated during consecutive cycles, using the same stimulation protocol, with highly purified urinary FSH (HP-FSH) in the first treatment study cycle and recombinant FSH (rFSH) in the second one. Patients in group 1 were treated according to a late low-dose technique, and WHO group II anovulatory patients (group 2) received chronic low-dose FSH therapy.
Results:Compared with HP-FSH, treatment with rFSH in group 2 required significantly less ampules of drug to induce follicular development but resulted in significantly higher plasma levels of estradiol and inhibin A on the day of human chorionic gonadotropin injection. No differences were found when both treatment modalities were compared in group 1.
Conclusions:rFSH is more efficacious than urinary HP-FSH for ovulation induction in WHO group II anovulatory infertile patients as assessed by follicular development, hormonal levels, and the amount of FSH required.
low-dose follicle-stimulating hormone (FSH) therapy; induction of ovulation; recombinant FSH; WHO group II anovulation
Objective. There is an asymmetric allocation of technology and other resources for infertility services. Intrauterine insemination (IUI) is a process of placing washed spermatozoa transcervically into the uterine cavity for treatment of infertility. This is a review of literature for the potential use of IUI as a basic infertility treatment in technology-limited settings. Study design. Review of articles on treatment of infertility using IUI. Results. Aspects regarding the use of IUI are reviewed, including ovarian stimulation, semen parameters associated with good outcomes, methods of sperm preparation, timing of IUI, and number of inseminations. Implications of the finding in light of the needs of low-technology medical settings are summarized. Conclusion. The reviewed evidence suggests that IUI is less expensive, less invasive, and comparably effective for selected patients as a first-line treatment for couples with unexplained or male factor infertility. Those couples may be offered three to six IUI cycles in technology-limited settings.
Purpose: This multicenter study was carried out to compare the efficacy of intrauterine insemination (IUI) and intraperitoneal insemination (IPI) associated with multiple follicular development as treatment for unexplained infertility.
Method: A total of 205 couples completed the trial. Sixty-seven couples underwent treatment with IPI (group A) and 138 couples underwent treatment with IUI (group B).
Results: Clinical pregnancy was obtained in 23 couples in group A (pregnancy rate: 34.3%) and in 36 couples in group B (pregnancy rate: 26.1%). No significant difference was observed between group A and group B. As for the evolution of pregnancies and the incidence of twin pregnancies, no significant difference was observed between the two groups.
Conclusions: Because IUI and IPI allow us to obtain same results and IPI is more invasive than IUI, the latter technique can be considered the method of choice and IPI should be used when IUI is difficult to perform, as in the presence of a tight cervical canal.
intraperitoneal insemination; intrauterine insemination; multicenter study; multiple follicular development; unexplained infertility
In in vitro fertilization (IVF) and intracytoplasmatic sperm injection (ICSI) treatment a large drop is present between embryo transfer and occurrence of pregnancy. The implantation rate per embryo transferred is only 30%. Studies have shown that minor intrauterine abnormalities can be found in 11–45% of infertile women with a normal transvaginal sonography or hysterosalpingography. Two randomised controlled trials have indicated that detection and treatment of these abnormalities by office hysteroscopy after two failed IVF cycles leads to a 9–13% increase in pregnancy rate. Therefore, screening of all infertile women for intracavitary pathology prior to the start of IVF/ICSI is increasingly advocated. In absence of a scientific basis for such a policy, this study will assess the effects and costs of screening for and treatment of unsuspected intrauterine abnormalities by routine office hysteroscopy, with or without saline infusion sonography (SIS), prior to a first IVF/ICSI cycle.
Multicenter randomised controlled trial in asymptomatic subfertile women, indicated for a first IVF/ICSI treatment cycle, with normal findings at transvaginal sonography. Women with recurrent miscarriages, prior hysteroscopy treatment and intermenstrual blood loss will not be included. Participants will be randomised for a routine fertility work-up with additional (SIS and) hysteroscopy with on-the-spot-treatment of predefined intrauterine abnormalities versus the regular fertility work-up without additional diagnostic tests. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months of IVF/ICSI treatment after randomisation. Secondary study outcome parameters are the cumulative implantation rate; cumulative miscarriage rate; patient preference and patient tolerance of a SIS and hysteroscopy procedure. All data will be analysed according to the intention-to-treat principle, using univariate and multivariate logistic regression and cox regression. Cost-effectiveness analysis will be performed to evaluate the costs of the additional tests as routine procedure. In total 700 patients will be included in this study.
The results of this study will help to clarify the significance of hysteroscopy prior to IVF treatment.
Hysteroscopy; Subfertility; IVF
We present our early experience with gamete intrafallopian transfer (GIFT) and direct intraperitoneal insemination (DIPI) combined with intrauterine insemination (IUI), two recently described methods of assisting conception in patients with patent fallopian tubes. Sixty-nine patients (93 cycles) were entered into the study. Thirty-three patients (51 cycles) entered the DIPI/IUI programme and 36 patients (42 cycles) entered the GIFT programme. The mean age, duration and aetiology of infertility were similar in both groups. In the GIFT programme 12 pregnancies occurred, which is a 29% pregnancy rate per cycle and a 33% pregnancy rate per patient. In the DIPI/IUI programme only 3 pregnancies occurred, being a 6% pregnancy rate per cycle and a 9% pregnancy rate per patient. With the live birth rate of in vitro fertilization (IVF) being 12% per embryo transfer, we conclude that GIFT is more successful than either DIPI/IUI or IVF in patients with patent fallopian tubes. Further controlled studies are required to assess the future role of DIPI/IUI in clinical practice.
Purpose: Our purpose was to determine if pregnancy rates(PRs) for hMG (human menopausalgonadotropin)-stimulated IVF-ET (in vitro ferilization-embryo transfer) can beincreased by estradiol (E2) supplementation from the earlyproliferative phase to the late secretory phase of theendometrium.
Method: Eighty-one infertile women with pure tubal factorwere randomized into two groups. One group received noE2 supplementation (control group) and the other receivedoral E2 supplementation (2 mg two times daily) from theearly proliferative phase starting on the third day of themenstrual cycle to the late secretory phase of theendometrium, with hMG stimulation for ovulation induction startingon the sixth day of the menstrual cycle.
Results: In 85 cycles, at least one embryo was transferred.Compared with the control group (n = 27 cycles), the E2supplementation group (n = 58 cycles) had a significantlyhigher PR (control, 25.9%, versus E2 supplementation,48.3%) and IR per ET (control, 10%, versus E2supplementation, 26%), but FRs per retrieved oocytes were notstatistically different between the two groups (control, 74%, versusE2 supplementation group, 73%). Four spontaneousabortions occurred in the E2 supplementation group, and onecase in the control group. Ectopic pregnancy occurred inone case in the control group.
Conclusions: Clinical PRs and IRs in the E2supplementation group were significantly higher than in the controlgroup, while FRs in the control group did not differstatistically from the E2 supplementation group. This suggests thatE2 supplementation from the early proliferative phase to thelate secretory phase of the endometrium in hMG-stimulatedIVF-ET increases the receptivity of the endometrium fortransferred embryos and clinical PRs.
in vitro fertilization-embryo transfer; estradiol valerate
To compare the efficacy of intrafollicular sperm injection (IFI) versus intrauterine insemination (IUI) in the treatment of subfertility.
38 couples suffering primary or secondary subfertility contributed a total of 47 IUI or IFI cycles, 26 by IUI and 21 by IFI. Folliculogenesis, ovulation triggering, and IUI or IFI were performed. Motile spermatozoa were inseminated into the uterine cavity for IUI or injected into pre-ovulatory follicles for IFI. The rate of biochemical and clinical pregnancy was assessed.
The rate of biochemical pregnancy/cycle for IUI was 11 % as compared to 38 % for IFI (p = 0.04). The rate of clinical pregnancy/cycle for IUI was 11 % as compared to 29 % for IFI (p = 0.26). The rate of twin pregnancy and miscarriage was low and no high order multiple gestation was observed. The rate of ectopic tubal pregnancy/cycle for IUI was 0 % as compared to 9 % for IFI (p = 0.19); no ovarian pregnancy was observed. When the analysis was confined to IFI cycles in which 2.68-6.65 million motile spermatozoa were injected/follicle (n = 10), a rate of 60 % clinical pregnancy/cycle was observed, of which 2 were ectopic.
Under the conditions described herein, IFI was more effective than IUI at achieving pregnancy.
Intrafollicular sperm injection; Intrauterine insemination
Women with primary infertility and no obvious pelvic pathology on clinical evaluation and imaging are either treated empirically or further investigated by laparoscopy.
The role of diagnostic laparoscopy in women who fail to conceive after empirical treatment with ovulation induction and intrauterine insemination was evaluated.
SETTINGS AND DESIGN:
Retrospective study at a private infertility center.
MATERIALS AND METHODS:
A study of patients who underwent diagnostic laparoscopy between 1st January 2001 and 31st December 2008 was performed. Those patients who had no detectable pathology based on history, physical examination, and ultrasound and had treatment for three or more cycles in the form of ovulation induction and IUI were included in the study. Moderate and severe male factor infertility and history of any previous surgery were exclusion criteria.
STATISTICAL ANALYSIS USED:
Data were statistically analyzed using Statistics Package for Social Sciences (ver. 16.0; SPSS Inc., Chicago).
Of the 127 women who underwent diagnostic laparoscopy and hysteroscopy, 87.4% (n = 111) of patients had positive findings. Significant pelvic pathology (moderate endometriosis, pelvic inflammatory disease, and tubal pathology) was seen in 26.8% of cases.
One in four women had significant pelvic pathology where treatment could possibly improve future fertility. Diagnostic laparoscopy has a role in infertile women with no obvious abnormality before they proceed to more aggressive treatments.
Female infertility; intrauterine insemination; laparoscopy
There are different factors that influence treatment outcome after ovarian stimulation and timed-intercourse or intrauterine insemination (IUI). After patient age, it has been suggested that timing of insemination in relation to ovulation is probably the most important variable affecting the success of treatment. The objective of this study is to study the value of human chorionic gonadotropin (hCG) administration and occurrence of luteinizing hormone (LH) surge in timing insemination on the treatment outcome after follicular monitoring with timed-intercourse or intrauterine insemination, with or without ovarian stimulation.
Retrospective analysis of 2000 consecutive completed treatment cycles (637 timed-intercourse and 1363 intrauterine insemination cycles). Stimulation protocols included clomiphene alone or with FSH injection, letrozole (an aromatase inhibitor) alone or with FSH, and FSH alone. LH-surge was defined as an increase in LH level ≥200% over mean of preceding two days. When given, hCG was administered at a dose of 10,000 IU. The main outcome was clinical pregnancy rate per cycle.
Higher pregnancy rates occurred in cycles in which hCG was given. Occurrence of an LH-surge was associated with a higher pregnancy rate with clomiphene treatment, but a lower pregnancy rate with FSH treatment.
hCG administration is associated with a favorable outcome during ovarian stimulation. Awaiting occurrence of LH-surge is associated with a better outcome with CC but not with FSH treatment.
The purpose of the study was to determine the incidence of survivin gene expression in human granulosa cells during ovarian stimulation in Greek women with normal FSH levels, undergoing IVF or ICSI and to discover any correlation between levels of gene expression and clinical parameters, efficacy of ovulation or outcomes of assisted reproduction.
Twenty nine women underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus–mature oocyte complexes were denuded and the granulosa cells were analyzed for each patient separately using quantitative reverse transcription polymerase chain reaction analysis for survivin gene expression with internal standard the ABL gene.
The ABL and survivin mRNA were detected in granulosa cells in 93.1%. The expression levels of survivin were significantly lower in normal women (male infertility factor) compared to women with tubal infertility factor (p = 0.007). There was no additional statistically significant correlation between levels of survivin expression and estradiol levels or dosage of FSH for ovulation induction or number of dominant follicles aspirated or number of retrieved oocytes or embryo grade or clinical pregnancy rates respectively.
High levels of survivin mRNA expression in luteinized granulosa cells in cases with tubal infertility seem to protect ovaries from follicular apoptosis. A subpopulation of patients with low levels of survivin mRNA in granulosa cells might benefit with ICSI treatment to bypass possible natural barriers of sperm-oocyte interactions.
Granulosa cells; Infertile patients; Survivin; IVF; ICSI
To study the efficacy of the aromatase inhibitor letrozole in controlled ovarian hyperstimulation (COH).
Material and methods
In this prospective simply randomized clinical trial, one hundred forty patients with unexplained infertility undergoing intrauterine insemination (IUI) therapy were randomized to receive either letrozole or clomiphene citrate (CC)-gonadotropin. The patients were selected among patients referred to one university hospital and one private infertility clinic. A letrozole dose of 5 mg/day (n = 70) was given on days 3–7 of the menstrual cycles. Clomiphen citrate a dose of 100 mg/day was given like letrozole but combined with human menopausal gonadotropin (hMG) dose of 75 IU/ml administered every day starting on day 6. Ovulation was triggered with urinary hCG (10,000 IU) when the leading follicle(s) reached 18 mm in diameter. A single IUI was performed 36 hours later. The luteal phase was supplemented with micronized progesterone vaginally. Ovarian stimulation response (E2 levels and number of follicles) was primary outcome.
There were no differences in demographic characteristics between groups. The number of mature follicles (1.8 ± 0.7 vs. 2.46 ± 2.3; P = 0.042) and serum E2 level on the day of hCG (310 ± 135.4 vs. 1,670.7 ± 1021.8 pg/ml, respectively; P < 0.0001) were significantly lower in letrozole group. A significantly higher endometrial thickness was observed at the time of hCG administration in patients that received letrozole (9.7 ± 1.6 mm vs. 7.8 ± 2 mm; P < 0.001).Clinical pregnancy rates also were significantly higher in letrozole group (32.8% vs. 14.3%, respectively; P < 0.01).
The aromatase inhibitor letrozole appears to constitute a good alternative to CC-gonadotropin in patients with unexplained infertility undergoing COH cycles combined with IUI therapy.
Ovarian stimulation; Gonadotropin; Clomiphene citrate; Letrozole
Objective To compare the effectiveness of clomifene citrate and unstimulated intrauterine insemination with expectant management for the treatment of unexplained infertility.
Design Three arm parallel group, pragmatic randomised controlled trial.
Setting Four teaching hospitals and a district general hospital in Scotland.
Participants Couples with infertility for over two years, confirmed ovulation, patent fallopian tubes, and motile sperm.
Intervention Expectant management, oral clomifene citrate, and unstimulated intrauterine insemination.
Main outcome measures The primary outcome was live birth. Secondary outcome measures included clinical pregnancy, multiple pregnancy, miscarriage, and acceptability.
Results 580 women were randomised to expectant management (n=193), oral clomifene citrate (n=194), or unstimulated intrauterine insemination (n=193) for six months. The three randomised groups were comparable in terms of age, body mass index, duration of infertility, sperm concentration, and motility. Live birth rates were 32/193 (17%), 26/192 (14%), and 43/191 (23%), respectively. Compared with expectant management, the odds ratio for a live birth was 0.79 (95% confidence interval 0.45 to 1.38) after clomifene citrate and 1.46 (0.88 to 2.43) after unstimulated intrauterine insemination. More women randomised to clomifene citrate (159/170, 94%) and unstimulated intrauterine insemination (155/162, 96%) found the process of treatment acceptable than those randomised to expectant management (123/153, 80%) (P=0.001 and P<0.001, respectively).
Conclusion In couples with unexplained infertility existing treatments such as empirical clomifene and unstimulated intrauterine insemination are unlikely to offer superior live birth rates compared with expectant management.
Trial registration ISRCT No: 71762042
Purpose:Our purpose was to demonstrate the feasibility of the routine aspiration of supernumerary follicles in infertile patients with imminent polyovulation after ovulation induction with gonadotropins and to examine its effect on the frequency of cycle cancellation and on the (multiple) pregnancy rate.
Methods:The data on 796 treatment cycles, performed between 1989 and 1996 on 410 infertile couples, were analyzed retrospectively. From October 1992, whenever necessary, supernumerary ovarian follicles were selectively aspirated transvaginally under ultrasound guidance to prevent the ovulation of more than three follicles. Thereafter, intrauterine insemination was performed.
Results:After the adoption of transvaginal ultrasound-guided aspiration of supernumerary follicles into the treatment protocol in October 1992, the number of canceled cycles (P < 0.0001) and the multiple pregnancy rate (P < 0.01) were significantly reduced compared to those previously. The overall pregnancy rate remained stable. No ovarian hyperstimulation syndrome requiring hospitalization was noted, and no complications resulting from the follicle aspiration were registered.
Conclusions:Transvaginal ultrasound-guided aspiration of supernumerary ovarian follicles increases both the efficacy and the safety of ovulation induction with gonadotropins. Because of the limited equipment required, this method represents an alternative for conversion of overstimulated cycles to more costly alternatives such as in vitro fertilization.
intrauterine insemination; ovulation induction; ultrasound-guided follicle puncture; ovarian stimulation; multiple pregnancy
Recombinant human follicle stimulating hormone (rFSH) and luteinizing hormone (LH), also known as follitropin alpha and lutropin alpha, are manufactured by genetic engineering techniques which ensure high quality and batch to batch consistency. Follitropin alpha can be used for controlled ovarian hyperstimulation in assisted reproduction, ovulation induction for WHO group I and II anovulatory infertility and in men with hypogonadotrophic hypogonadism (HH) or idiopathic oligo-asthenospermia. Current evidence suggests superiority of urinary human menopausal gonadotropin (HMG) over follitropin alpha in controlled ovarian hyperstimulation for IVF in terms of live birth rate per couple. Addition of lutropin to follitropin alpha in an unselected IVF population does not appear to confer any benefit; however, it may have a role in ovulation induction in women with hypothalamic hypogonadism. Urinary HMG preparations (especially currently available highly purified preparations) are more cost effective than rFSH in terms of cost per ongoing pregnancy. However, women using rFSH injection pen devices have higher levels of satisfaction as compared to those using urinary HMG by means of conventional syringes.
infertility; follicle stimulating hormone; luteinizing hormone; follitropin alpha; lutropin alpha; in-vitro fertilization; urinary gonadotrophins
The purpose of the study was to determine the incidence of gene expression of Oct-4 and DAZL, which are typical markers for stem cells, in human granulosa cells during ovarian stimulation in women with normal FSH levels undergoing IVF or ICSI and to discover any clinical significance of such expression in ART.
Twenty one women underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus–mature oocyte complexes were denuded separately and granulosa cells were analyzed for each patient separately using quantitative reverse-transcription–polymerase chain reaction analysis for Oct-4 and DAZL gene expression with G6PD gene as internal standard.
G6PD and Oct-4 mRNA was detected in the granulosa cells in 47.6% (10/21). The median of Oct-4 mRNA/G6PD mRNA was 1.75 with intra-quarteral range from 0.10 to 98.21. The OCT-4 mRNA expression was statistically significantly correlated with the number of oocytes retrieved; when the Oct-4 mRNA expression was higher, then more than six oocytes were retrieved (p=0.037, Wilcoxon rank-sum). No detection of DAZL mRNA was found in granulosa cells. There was no additional statistically significant correlation between the levels of Oct-4 expression and FSH basal levels or estradiol peak levels or dosage of FSH for ovulation induction. No association was found between the presence or absence of Oct-4 mRNA expression in granulosa cells and ovarian response to gonadotropin stimulation. Also, no influence on pregnancy was observed between the presence or absence of Oct-4 mRNA expression in granulosa cells or to its expression levels accordingly.
Expression of OCT-4 mRNA, which is a typical stem cell marker and absence of expression of DAZL mRNA, which is a typical germ cell marker, suggest that a subpopulation of luteinized granulosa cells in healthy ovarian follicles (47.6%) consists of stem cells, which are not originated from primordial germ cells. Absence of Oct-4 gene expression in more than half of the cases means probably the end of the productive journey of these cells, towards the oocyte.
Granulosa cells; Infertile patients; Oct-4; DAZL; Stem cells; IVF