Safety Of Ovarian Stimulation Research Articles

Assessing ovarian stimulation with letrozole and levonorgestrel intrauterine system after combined fertility-sparing approach for atypical endometrial lesions: a retrospective case-control study

Research questionIs ovarian stimulation with levonorgestrel intrauterine system (LNG-IUS) in situ and co-treatment with letrozole safe and effective in patients undergoing fertility-sparing combined treatment for atypical endometrial hyperplasia (AEH) or early endometrial cancer limited to the endometrium? DesignRetrospective case-control study recruiting women who had undergone fertility-sparing ‘combined’ treatment and ovarian stimulation with letrozole and LNG-IUS in situ. The ‘three steps’ hysteroscopic technique was used. Once complete response was achieved, the ovaries were stimulated, and mature oocytes cryopreserved. The LNG-IUS was removed, and embryos transferred. A comparative analysis was conducted between the two control groups of the initial outcomes of ART (number of oocytes and MII oocytes retrieved): healthy infertile women undergoing ovarian stimulation for IVF/ICSI (control group A); and patients diagnosed with breast cancer who underwent ovarian stimulation with letrozole (control group B). ResultsOf the 75 patients analysed, 15 underwent oocyte cryopreservation after achieving a complete response to fertility-sparing treatment (study group); 30 patients in control group A and B, respectively. No statistically significant differences were observed in retrieved oocytes and mature oocytes between the study and control groups. In the nine patients who underwent embryo transfer, clinical pregnancy (55.6%), cumulative live birth (44.4%) and miscarriage (20%) rates were reported. In three patients with AEH, recurrence occurred (12%) at 3, 6 and 16 months after removing the LNG-IUS to attempt embryo transfer, respectively. ConclusionFertility-sparing hysteroscopic combined treatment and subsequent ovarian stimulation with letrozole and LNG-IUS in situ could be suggested to women with AEH or early endometrial cancer who ask for future fertility preservation.

Ovarian Stimulation Strategies for Intrauterine Insemination in Couples with Unexplained Infertility - A Systematic Review and Individual Participant Data Meta-analysis

Background: Intrauterine insemination with ovarian stimulation (IUI-OS) is a first-line treatment for couples with unexplained infertility. Individual participant data meta-analysis (IPD-MA) is the gold standard for evidence synthesis. Aim: To compare the effectiveness and safety of ovarian stimulation with gonadotrophin, Letrozole and clomiphene citrate (CC) and to explore treatment-covariate interactions for important baseline characteristics in women undergoing IUI. Method: We searched electronic databases including PubMed, MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL). We included randomised controlled trials (RCTs) comparing IUI-OS with gonadotropins, Letrozole or CC among couples with unexplained infertility. We excluded dose comparing studies of the same drug. We contacted the authors of eligible RCTs to share the IPD and established the IUI IPD-MA collaboration. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. We used a one-stage approach using a random effects model. Results: Six RCTs (n= 2299) provided IPD. Gonadotropins increased the chance of a live birth compared to both CC (5 RCTs, 1946 women, RR 1.28, 95%CI 1.10 to 1.49, I2 = 25%, moderate-quality evidence) whereas there was insufficient evidence of a difference between Letrozole and CC (1 RCT, 599 women, RR 0.77 95%CI 0.58 to 1.03). Gonadotropins increased the risk of a multiple pregnancy compared to both CC (4 RCTs, 1696 women, RR 2.17, 95%CI 1.33 to 3.55, I2 = 69%, low-quality evidence) whereas there was insufficient evidence of a difference between Letrozole and CC (1 RCT, 599 women, RR 0.71, 95%CI 0.33 to 1.56). No strong evidence on the treatment-covariate interactions (female age, BMI or primary versus secondary infertility) was found. Conclusion: Gonadotropins increased the chance of a live birth compared to both CC and Letrozole but also increased the chance of a multiple pregnancy. Further RCTs comparing Letrozole and other interventions in couples with unexplained infertility are needed.

Ovarian stimulation strategies for intrauterine insemination in couples with unexplained infertility: a systematic review and individual participant data meta-analysis.

BACKGROUNDIntrauterine insemination with ovarian stimulation (IUI-OS) is a first-line treatment for unexplained infertility. Gonadotrophins, letrozole and clomiphene citrate (CC) are commonly used agents during IUI-OS and have been compared in multiple aggregate data meta-analyses, with substantial heterogeneity and no analysis on time-to-event outcomes. Individual participant data meta-analysis (IPD-MA) is considered the gold standard for evidence synthesis as it can offset inadequate reporting of individual studies by obtaining the IPD, and allows analyses on treatment–covariate interactions to identify couples who benefit most from a particular treatment.OBJECTIVE AND RATIONALEWe performed this IPD-MA to compare the effectiveness and safety of ovarian stimulation with gonadotrophins, letrozole and CC and to explore treatment–covariate interactions for important baseline characteristics in couples undergoing IUI.SEARCH METHODSWe searched electronic databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO from their inception to 28 June 2021. We included randomized controlled trials (RCTs) comparing IUI-OS with gonadotrophins, letrozole and CC among couples with unexplained infertility. We contacted the authors of eligible RCTs to share the IPD and established the IUI IPD-MA Collaboration. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. Secondary outcomes were other reproductive outcomes, including time to conception leading to live birth. We performed a one-stage random effects IPD-MA.OUTCOMESSeven of 22 (31.8%) eligible RCTs provided IPD of 2495 couples (62.4% of the 3997 couples participating in 22 RCTs), of which 2411 had unexplained infertility and were included in this IPD-MA. Six RCTs (n = 1511) compared gonadotrophins with CC, and one (n = 900) compared gonadotrophins, letrozole and CC. Moderate-certainty evidence showed that gonadotrophins increased the live birth rate compared to CC (6 RCTs, 2058 women, RR 1.30, 95% CI 1.12–1.51, I2 = 26%). Low-certainty evidence showed that gonadotrophins may also increase the multiple pregnancy rate compared to CC (6 RCTs, 2058 women, RR 2.17, 95% CI 1.33–3.54, I2 = 69%). Heterogeneity on multiple pregnancy could be explained by differences in gonadotrophin starting dose and choice of cancellation criteria. Post-hoc sensitivity analysis on RCTs with a low starting dose of gonadotrophins (≤75 IU) confirmed increased live birth rates compared to CC (5 RCTs, 1457 women, RR 1.26, 95% CI 1.05–1.51), but analysis on only RCTs with stricter cancellation criteria showed inconclusive evidence on live birth (4 RCTs, 1238 women, RR 1.15, 95% CI 0.94–1.41). For multiple pregnancy, both sensitivity analyses showed inconclusive findings between gonadotrophins and CC (RR 0.94, 95% CI 0.45–1.96; RR 0.81, 95% CI 0.32–2.03, respectively). Moderate certainty evidence showed that gonadotrophins reduced the time to conception leading to a live birth when compared to CC (6 RCTs, 2058 women, HR 1.37, 95% CI 1.15–1.63, I2 = 22%). No strong evidence on the treatment–covariate (female age, BMI or primary versus secondary infertility) interactions was found.WIDER IMPLICATIONSIn couples with unexplained infertility undergoing IUI-OS, gonadotrophins increased the chance of a live birth and reduced the time to conception compared to CC, at the cost of a higher multiple pregnancy rate, when not differentiating strategies on cancellation criteria or the starting dose. The treatment effects did not seem to differ in women of different age, BMI or primary versus secondary infertility. In a modern practice where a lower starting dose and stricter cancellation criteria are in place, effectiveness and safety of different agents seem both acceptable, and therefore intervention availability, cost and patients’ preferences should factor in the clinical decision-making. As the evidence for comparisons to letrozole is based on one RCT providing IPD, further RCTs comparing letrozole and other interventions for unexplained infertility are needed.

O-180 Oocyte vitrification for fertility preservation does not delay the initiation of neoadjuvant chemotherapy for breast cancer

Abstract Study question Does oocyte vitrification for fertility preservation (FP) delay the initiation of neoadjuvant chemotherapy for breast cancer? Summary answer The indication of neoadjuvant chemotherapy for breast cancer should not be considered as an impediment to urgent oocyte vitrification for FP. What is known already FP is considered as one of the most important issues to address for young breast cancer patients. Cryopreservation of oocytes or embryos may be considered after controlled ovarian hyperstimulation (COH) or in vitro maturation (IVM). Pregnancies have been reported after reutilization of oocytes frozen following both procedures. Although oocyte competence is better after COH, this strategy requires on average 13 days to be achieved. In addition, the safety of ovarian stimulation before tumor removal is currently not formally established. In case of neoadjuvant chemotherapy, the risk-benefit balance of COH is not well known. Study design, size, duration Retrospective cohort study including all breast cancer patients eligible for oocyte vitrification following COH or IVM before initiation of neoadjuvant chemotherapy between January 2016 and December 2020. Participants/materials, setting, methods Inclusion criteria were: female patients with confirmed non metastatic breast cancer, 18 to 40 years of age, with indication of neoadjuvant chemotherapy, who have had oocyte retrieval for FP after COH or IVM +/- cryopreservation of ovarian tissue. Various time-points related to cancer diagnosis, FP or chemotherapy were obtained from medical record review. Main results and the role of chance A total of 198 patients with confirmed breast cancer who had oocyte retrieval following COH (n = 57) or IVM +/- cryopreservation of ovarian tissue (n = 141) for FP prior to neoadjuvant chemotherapy were included. Although women in IVM group were significantly younger as compared to patients who underwent COH (31.7 ± 4.2 vs. 33.3 ± 4.0 years, p = 0.019), ovarian reserve parameters, BMI and cancer stage did not differ between the two groups. Overall, the average time from cancer diagnosis to chemotherapy start was similar between patients having undergone COH or IVM before oocyte vitrification (37.3 ± 13.8 vs. 36.9 ±13.5 days in COH and IVM groups respectively, p=0.857). Limitations, reasons for caution The time from referral to FP consultation may have influenced the type of FP. In addition, the retrospective nature of the present analysis may constitute a limitation. Moreover, the efficiency and security of the different FP strategies used has not been analysed. Wider implications of the findings Oocyte vitrification following COH or IVM was not associated with delayed breast cancer treatment in the neoadjuvant setting, so long as there was a prompt FP referral. Young patients undergoing neoadjuvant chemotherapy should be informed of these findings to avoid unnecessary anxiety due to concern for delays. Trial registration number Not applicable

Individualized follitropin delta dosing reduces OHSS risk in Japanese IVF/ICSI patients: a randomized controlled trial

Research questionThis study aimed to establish the efficacy and safety of ovarian stimulation with a follitropin delta individualized fixed-dose regimen based on serum anti-Müllerian hormone (AMH) concentration and body weight versus conventional follitropin beta dosing in Japanese women. DesignThis randomized, controlled, assessor-blind, multicentre, non-inferiority trial was conducted in 347 Japanese IVF/intracytoplasmic sperm injection patients. They were randomized to individualized follitropin delta (AMH <15 pmol/l: 12 µg/day; AMH ≥15 pmol/l: 0.10–0.19 µg/kg/day; minimum 6 µg/day; maximum 12 µg/day) or conventional follitropin beta (150 IU/day for the first 5 days, with potential subsequent dose adjustments). The primary end-point was the number of oocytes retrieved with a pre-specified non-inferiority margin (−3.0 oocytes). ResultsThe primary trial objective was met, as non-inferiority was established for number of oocytes retrieved for individualized follitropin delta dosing compared with conventional follitropin beta dosing (9.3 versus 10.5; lower boundary of 95% confidence interval −2.3). The occurrence of ovarian hyperstimulation syndrome (OHSS) was reduced to approximately half with individualized compared with conventional dosing, with an incidence of 11.2% versus 19.8% (P = 0.021) for OHSS of any grade and 7.1% versus 14.1% (P = 0.027) for moderate/severe OHSS. The live birth rate per started cycle was 23.5% for individualized dosing and 18.6% for conventional dosing. ConclusionsDosing with individualized follitropin delta in Japanese women is non-inferior to conventional dosing with follitropin beta for number of oocytes retrieved. The individualized approach shows a favourable benefit–risk profile, providing a statistically significant and clinically relevant reduction in the incidence of OHSS, without compromising live birth rates.

Fertility preservation before hematopoetic stem cell transplantation: a case series of women with GATA binding protein 2 deficiency, dedicator of cytokinesis 8 deficiency, and sickle cell disease

ObjectiveTo describe fertility characteristics, outcomes of oocyte cryopreservation cycles, and safety of ovarian stimulation in patients with GATA binding protein 2 (GATA2) deficiency, dedicator of cytokinesis 8 (DOCK8) deficiency, and sickle cell disease (SCD) preparing for hematopoetic stem cell transplantation (HSCT).DesignRetrospective case series.SettingThe National Institutes of Health.Patient(s)Female patients with GATA2 deficiency, DOCK8 deficiency, and SCD aged between 13 and 38 years.Intervention(s)None.Main Outcome Measure(s)Demographic and ovarian reserve parameters, stimulation outcomes, and adverse event occurrences were collected through chart review. Descriptive statistics were used to identify trends within disease subcategories.Result(s)Twenty-one women with GATA2 deficiency, DOCK8 deficiency, and SCD underwent fertility preservation prior to HSCT. Patients with DOCK8 deficiency had the lowest mean age (16.5 years old) and antimüllerian hormone (0.85 ng/mL). Patients with GATA2 deficiency had the highest antral follicle count and antimüllerian hormone (25.77 and 5.07 ng/mL, respectively). Baseline follicle-stimulating hormone, luteinizing hormone, and estradiol were comparable between the cohorts. The duration of stimulation was similar (10.43 to 11.25 days) across all groups. Comparable peak estradiol levels were achieved across the cohorts. Patients with SCD had the highest mature (MII) oocyte yield (10.71). Three patients experienced complications related to stimulation: pain crisis in a patient with SCD, pulmonary embolism, and zero oocytes cryopreserved in a patient with GATA2 deficiency.Conclusion(s)This study offers insight into controlled ovarian stimulation in patients with these conditions prior to HSCT. Oocyte cryopreservation can be performed successfully, although adverse events must be considered. Following the outcomes of gamete use in this cohort will serve to further our knowledge of the true reproductive potential of this population.

Effectiveness and safety of follitropin alfa (Ovaleap\xae) for ovarian stimulation using a GnRH antagonist protocol in real-world clinical practice: a multicenter, prospective, open, non-interventional assisted reproductive technology study

BackgroundThe use of recombinant human follicle-stimulating hormone (r-hFSH) in ovarian stimulation protocols for infertility treatment in assisted reproductive technology (ART) clinical practice is well established. More recent advancements include the availability of biosimilar r-hFSH products, which expand the choices available to healthcare practitioners and patients. Better understanding of how such a product contributes to routine clinical practice is valuable to help prescribers make informed treatment choices. The objective of this study was to examine the effectiveness and safety of ovarian stimulation (OS) with follitropin alfa (Ovaleap®) for routine IVF or intracytoplasmic sperm injection treatment in gonadotropin-releasing hormone (GnRH) antagonist cycles in real-world ART clinical practice.MethodsThis non-interventional, multicenter, prospective study was initiated in 34 specialized reproductive medicine centers in Germany. Eligible women were 18–40 years old with a body mass index < 30 kg/m2, menstrual cycle 24–35 days and anti-Müllerian hormone ≥1 ng/mL, who were undergoing a first OS cycle exclusively with Ovaleap® during routine ART using a GnRH antagonist protocol. Primary effectiveness outcomes were number of retrieved oocytes after OS and clinical pregnancy rate (CPR). Secondary outcomes included fertilization rate, number of transferred embryos, live birth delivery rate, safety, and user satisfaction with the Ovaleap® pen.Result(s)Of 507 women screened, 463 received at least 1 dose of Ovaleap® and 439 had Visit 2 data (per protocol population; PPP). The mean(±SD) number of retrieved oocytes was 11.8 ± 7.2 (PPP). The CPR among women with documented embryo transfer was 41.3% (158/383), resulting in a live birth delivery rate of 31.6% (138/437) among PPP patients with available follow-up information. Overall, 8.6% (40/463) of women reported ≥1 adverse drug reaction. Ovarian hyperstimulation syndrome occurred in 23 (5.0%) patients, rated mild in 14 (3.0%), moderate in 8 (1.7%), and severe in 1 (0.2%). Patients reported high user satisfaction and high convenience with use of the Ovaleap® pen.ConclusionThe effectiveness and safety of OS with Ovaleap® in a GnRH antagonist protocol were extended to real-world ART clinical practice for the first time.Trial registrationRegistered on 22 June 2016 (retrospectively registered) at ClinicalTrials.gov (NCT02809989).

Abstract P5-15-02: Safety of letrozole-gonadotropin controlled ovarian stimulation protocol in women with breast cancer undergoing fertility preservation before or after tumor resection via embryo or oocyte cryopreservation: A prospective cohort study

Abstract Purpose: We have previously described the concurrent use of aromatase inhibitors to reduce estrogen exposure in women with breast cancer undergoing controlled ovarian stimulation (COS) with gonadotropins for fertility preservation (FP) via oocyte or embryo cryopreservation. To purpose of this study was to investigate the impact of this letrozole-gonadotropin COS protocol on survival in women who underwent fertility preservation before or after breast surgery. Patients and Methods: A total of 364 women with stage ≤3 breast cancer, who pursued FP consultation or FP treatments at our institution were prospectively evaluated. Of those, 146 elected to undergo COS with letrozole and gonadotropins for FP (120 prior to chemotherapy and 26 after chemotherapy). The remaining 218 patients elected to not to undergo a fertility-preserving procedure and served as controls. Result(s): Demographic information and tumor characteristics at enrollment were similar between patients who pursued COS with letrozole and gonadotropins (COS group) and control groups. Table 1. Demographics and tumor characteristics of patients who pursued fertility preservation vs. controls Treatment Group (n=120)Control Group (n=218)P-valueAge at FP consultation (years)35.2±4.537.0±5.10.03Age at cancer diagnosis (years)34.8±4.534.9±4.70.88BMI (kg/m2)22.8±3.723.1±3.90.56Node involvement (%)34480.02Tumor size (cm) Mean±SD1.8 ±1.21.9±1.90.62&amp;lt;267660.592-53130 &amp;gt;523 Lymphovascular space invasion (%)31370.44Histologic grade 1-240391.0035759 Estrogen receptor positive (%)82770.27HER-2/neu positive (%)35330.78Adjuvant tamoxifen use (%)89871.00Length of follow-up (years, Mean±SD)5.0±2.16.9±3.6&amp;lt;0.001 The median follow-up after diagnosis was 4.9 years in COS and 6.2 years in the control group. In the COS group, the hazard ratio (HR) for recurrence after IVF was 0.77 (95% CI: 0.28, 2.13) and the survival was not compromised compared with controls (P=0.61). In the COS group, survival was not different between patients with ER-positive and ER-negative breast cancer (P=0.75) and between patients who underwent COS before and after tumor resection (P=0.56). The survival was also not different between patients who pursued COS before and after chemotherapy (P=0.57). Conclusion(s): Here we presented the largest prospective data with longest follow up on the safety of ovarian stimulation in women with breast cancer. COS with letrozole and gonadotropins for FP is unlikely to cause substantially increased recurrence risk in breast cancer, even in patients who have not yet undergone breast surgery. Larger studies are needed to confirm the findings from the subgroup analysis. Support: Supported by NIH RO1 HD053112. Citation Format: Kutluk Oktay, Jayeon Kim, Giuliano Bedoschi, Volkan Turan. Safety of letrozole-gonadotropin controlled ovarian stimulation protocol in women with breast cancer undergoing fertility preservation before or after tumor resection via embryo or oocyte cryopreservation: A prospective cohort study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-15-02.

Efficacy and safety of ovarian stimulation before chemotherapy in 205 cases

Ovarian stimulation and cryopreservation of fertilized oocytes before cancer therapy is the best established and efficient fertility preservation technique and should still be considered before chemotherapy. Within a short time frame of 2 weeks, between 8.6 (18-25 y) and 5.1 (36-40 y) fertilized oocytes can be cryopreserved.

Outcomes of New Quality Standards of Follitropin Alfa on Ovarian Stimulation

Human follicle-stimulating hormone (hFSH; follitropin alfa) can be employed therapeutically to induce ovarian follicular development in assisted reproduction treatments. Current recombinant hFSH (r-hFSH) preparations available for clinical use are labeled either in terms of the bioactivity expressed in international units (IU) or in mass (microg). Several clinical trials have tried to assess the clinical implications of the physicochemical improvements in the dosing of follitropin alfa filled by mass (FbM). The aim of this study was to perform a meta-analysis of previous studies in order to assess the efficacy and safety of ovarian stimulation using follitropin alfa FbM compared with follitropin alfa filled by international units (FbIU). A literature search was carried out in scientific databases to find published articles and abstracts comparing both hormone preparations. A fixed effects model meta-analysis was performed. The variables studied include the average dose (IU), days of treatment, estradiol peak, follicles >14 mm, number of extracted oocytes, number of embryos obtained, number of cases of ovarian hyperstimulation syndrome (OHSS), and clinical pregnancies. A total of six studies met the stated criteria and were included in the meta-analysis. In these studies, the average r-hFSH dose per patient was 230.29 IU less with administration of follitropin alfa FbM compared with FbIU, and the number of days of treatment was reduced by 0.48. In addition, a significantly greater number of oocytes (0.84) were extracted, more embryos (0.88) were obtained, and a higher peak level of estradiol (613.08 pmol/L) was achieved in the patients undergoing ovarian stimulation with follitropin alfa FbM. However, no statistically significant differences were observed in the number of follicles >14 mm, clinical pregnancies, or OHSS cases. Follitropin alfa FbM, a technologically modified formulation of r-hFSH, is as safe as follitropin alfa FbIU but requires a smaller dose over a shorter period to produce more oocytes and final embryos.

Safety of ovarian stimulation with letrozole and gonadotropins in breast cancer patients undergoing embryo or oocyte cryopreservation: a prospective controlled study

We have previously developed a protocol utilizing letrozole to minimize the rise of estradiol levels during ovarian stimulation (COH) in women with breast cancer. The objective of this study was to determine whether COH increase breast cancer recurrence. Prospective nonrandomized trial. Of the 215 women with breast cancer who were evaluated for fertility preservation, 79 elected to undergo COH with letrozole and gonadotropins for embryo or oocyte cryopreservation. The 136 patients who declined due to concerns about the safety, cost, and delay of chemotherapy served as controls. Stage 4 disease was excluded. Patients and/or their oncologists were contacted for recurrence information. To adjust for prognostic differences between the two groups, 10-year survival rates were calculated using Adjuvant Online. Groups were similar in terms of age at diagnosis (36.1 ± 3.8 vs. 35.6 ± 4.7, P=0.4), breast cancer prognostic parameters (tumor size, grade, number of positive lymph nodes, estrogen receptor status, her2-neu overexpression and vascular space invasion), and chemotherapy regimens. There was no difference in the projected 10 year relapse, breast cancer specific mortality or overall mortality at enrollment. There was a trend for higher estrogen receptor positivity in the COH group (P=0.08). Time between surgery and chemotherapy was longer for IVF patients (45.08 ± 31.64 vs. 33.46 ± 27.3 days, P<0.01). Peak E2 levels ranged from 58.4 to 1166 (mean 405.94 ± 256.64 pg/mL in COH patients. The median length of follow up after chemotherapy was 1.66 (range 0.29–10.28) years in the COH and 2.67 (range 0.29–9.5) years in the control group. There were 3 recurrences of contralateral breast cancers (2 distant, 1 locoregional) in the COH, and 11 in the control group (9 distant, 1 locoregional, 1 contralateral breast) (P=0.26) (Table). There was no significant difference in survival between the groups (Kaplan-Meier method, P=0.31, hazard ratio 0.53, 95% CI 0.17 to 1.8). Breast cancer recurrence or the incidence of invasive carcinoma in the contralateral breast does not appear to be increased after COH using letrozole and FSH for fertility preservation.Tabled 1Table.Letrozole group (n = 79)Control group (n = 141)Length of stimulation (day)9.87 ± 2.28NATotal gonodatropin dose (mlU/ml)1698.62 ± 818.76NANumber of oocytes retrieved10.3 ± 7.75NANumber of embryos or oocytes cryopreserved5.97 ± 4.97NALength of follow up (years) Mean2.18 ± 1.83.08 ± 2.17 Median1.662.67 Range0.29 – 10.280.29 – 9.5Patients with follow up information (%)79 (100)102 (75)Recurrence (%)3 (3.8)11 (8.1) Locoregional11 Distant29 Carcinoma in contralateral breast01Pregnancy (ongoing or delivery) Spontaneous13 After frozen embryo transfer8NA Open table in a new tab

Infertility: Late low-dose pure follicle stimulating hormone for ovarian stimulation in intra-uterine insemination cycles

At present, there is general agreement that ovarian stimulation improves pregnancy rates after intra-uterine insemination (IUI). Also, ovulation induction with gonadotrophins is associated with higher success rates than clomiphene citrate in IUI cycles. However, the drawbacks to the use of gonadotrophin stimulation before IUI include the risks of ovarian hyperstimulation and multiple gestation, and the relative cost of a treatment cycle in a view of the medication costs and the need for increased monitoring by hormone assays and ultrasonographic measurements. In the present prospective randomized trial, the efficacy and safety of ovarian stimulation with clomiphene citrate (50 mg/day for 5 days) and IUI (clomiphene/IUI group) were compared with those of late low-dose pure follicle stimulating hormone (FSH, 75 IU/day from day cycle 7 until the leading follicle reached > 17 mm in diameter) and IUI (FSH/IUI group) in ovulatory women who were infertile because of unexplained infertility (n = 40) or male subfertility (n = 60). The mean length of treatment in the FSH group was 6.4 +/- 2.5 days. Multiple follicular development was seen in 25% of clomiphene-stimulated cycles but only in 8% of those treated with FSH. Pregnancy rate per cycle in clomiphene/IUI and FSH/IUI groups was 4% (4/98) and 13% (12/94) respectively (P = 0.02). All pregnancies obtained were singleton. There were two and one clinical abortions in the clomiphene/IUI (50%) and FSH/IUI (8%) groups respectively. No patient developed ovarian hyperstimulation syndrome. Use of our therapeutic scheme, which proved to be efficacious, safe and economic for ovarian stimulation in IUI cycles, is advocated before the institution of in-vitro fertilization (IVF) or gamete intra-Fallopian transfer (GIFT) therapy in infertile patients with patient Fallopian tubes. This late low-dose technique of administering pure FSH is suitable for use in offices without immediate access to oestradiol results.