Immunomodulation for unexplained recurrent implantation failure: where are we now?

In brief: Immune dysfunction may contribute to or cause recurrent implantation failure. This article summarizes normal and pathologic immune responses at implantation and critically appraises currently used immunomodulatory therapies. Abstract: Recurrent implantation failure (RIF) may be defined as the absence of pregnancy despite the transfer of ≥3 good-quality blastocysts and is unexplained in up to 50% of cases. There are currently no effective treatments for patients with unexplained RIF. Since the maternal immune system is intricately involved in mediating endometrial receptivity and embryo implantation, both insufficient and excessive endometrial inflammatory responses during the window of implantation are proposed to lead to implantation failure. Recent strategies to improve conception rates in RIF patients have focused on modulating maternal immune responses at implantation, through either promoting or suppressing inflammation. Unfortunately, there are no validated, readily available diagnostic tests to confirm immune-mediated RIF. As such, immune therapies are often started empirically without robust evidence as to their efficacy. Like other chronic diseases, patient selection for immunomodulatory therapy is crucial, and personalized medicine for RIF patients is emerging. As the literature on the subject is heterogenous and rapidly evolving, we aim to summarize the potential efficacy, mechanisms of actions and side effects of select therapies for the practicing clinician.

Recurrent implantation failure in IVF: A Canadian Fertility and Andrology Society Clinical Practice Guideline.

Recurrent implantation failure (RIF) after IVF is a challenging topic for clinicians and can be a devastating reality for some patients with infertility. The purpose of this guideline from the Canadian Fertility and Andrology Society (CFAS) is to provide the most relevant evidence to date for the assessment and management of RIF. This guideline was developed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. This guideline recognizes the presence of heterogeneity in the definition of RIF. Recommendations are offered here on the investigation of RIF and management options that may increase the chance of a live birth.

Live birth rates remain stable in modified natural IVF despite low anti-Müllerian hormone: analysis of 638 cycles.

RESEARCH QUESTION: Do live birth rates (LBR) following modified natural IVF (mnIVF) differ according to serum anti-Müllerian hormone (AMH) concentration? DESIGN: Retrospective cohort study including 638 women aged ≤39 years starting their first mnIVF cycle at a university-affiliated private IVF centre. Patients were divided into three groups, by concentration of AMH: ≤0.5 ng/ml (25th percentile), 0.51-2.03 ng/ml (25-75th percentile, reference) and 2.04-6.56 ng/ml (75th percentile). Analyses were stratified by AMH percentile and the age of patients (<35, 35-39 years). Logistic regression assessed the impact of age and AMH percentile on outcomes. LBR was the primary outcome measure. RESULTS: LBR per started cycle were comparable across AMH percentiles (11.6%, 12.4% and 17.0% for the 25th, 25-75th and 75th percentile, respectively). No statistically significant difference was found between the three AMH groups with respect to cancellation, successful egg retrieval, embryo transfer, or biochemical and clinical pregnancy rates. Logistic regression analysis did not identify AMH percentile as a significant predictor of live birth. Compared with the reference group, the odds ratios (OR [95% confidence interval, CI]) for live birth in the <25th and >75th AMH percentile groups were 0.97 (0.54-1.76) and 1.41 (0.82-2.41), respectively. The results were the same regardless of age group (<35 years, 35-39 years). CONCLUSIONS: Serum AMH cannot be used to predict mnIVF outcomes. Patients in lower/upper AMH percentiles showed pregnancy and LBR comparable to patients with normal AMH.

Obesity and Reproduction.

OBJECTIVE: To provide a comprehensive review and evidence-based recommendations for the delivery of fertility care to women with obesity. OUTCOMES: The impact of obesity on fertility, fertility treatments, and both short and long-term maternal fetal outcomes was carefully considered. EVIDENCE: Published literature was reviewed through searches of MEDLINE and CINAHL using appropriate vocabulary and key words. Results included systematic reviews, clinical trials, observational studies, clinical practice guidelines, and expert opinions. VALUES: The Canadian Fertility & Andrology Society (CFAS) is a multidisciplinary, national non-profit society that serves as the voice of reproductive specialists, scientists, and allied health professionals working in the field of assisted reproduction in Canada. The evidence obtained for this guideline was reviewed and evaluated by the Clinical Practice Guideline (CPG) Committee of the CFAS under the leadership of the principal authors. BENEFITS, HARMS, AND COSTS: The implementation of these recommendations should assist clinicians and other health care providers in counselling and providing reproductive care to women with obesity. VALIDATION: This guideline and its recommendations have been reviewed and approved by the membership, the CPG Committee and the Board of Directors of the CFAS. SPONSORS: Canadian Fertility & Andrology Society. RECOMMENDATIONS: Twenty-one evidence based recommendations are provided. These recommendations specifically evaluate the impact of obesity on natural fertility, fertility treatments, and maternal-fetal outcomes. Strategies to lose weight and BMI cut-offs are also addressed.

Timing therapeutic donor inseminations in natural cycles: human chorionic gonadotrophin administration versus urinary LH monitoring.

This cohort study assessed whether timing therapeutic donor sperm inseminations (TDI) in natural cycles (NC) using ultrasound monitoring and ovulation trigger with human chorionic gonadotrophin (US/HCG) improves cumulative live birth rates (LBR) compared with detection of LH surge with urinary kits (u-LH). It included 232 normo-ovulatory women aged ≤40 years, undergoing 538 TDI in NC between 2011 and 2014. In the u-LH group (113 women, 267 cycles), TDI was performed the day following a positive test. In the US/HCG group (119 women, 271 cycles), ovulation was triggered with HCG when a follicle ≥17 mm was noted, and TDI performed 36 h later. The first three cycles were analysed per patient. Groups were comparable for baseline characteristics. Cumulative LBR were comparable between u-LH and US/HCG groups (31.47% versus 23.11%, respectively) (log-rank test). A generalized estimating equation analysis was performed to compare outcomes per cycle. The LBR per started cycle was comparable between the u-LH and US/HCG groups (12.4% versus 9.2%, respectively). Cancellation rate was significantly higher with u-LH (19.1% versus 11.4%, P = 0.011), but did not impact overall outcomes. In conclusion, urinary LH monitoring is as effective as ultrasound monitoring and ovulation trigger with HCG in TDI performed in NC.

Clomiphene Citrate versus Letrozole for Ovarian Stimulation in Therapeutic Donor Sperm Insemination.

AIM: To compare clomiphene citrate (CC) and letrozole for ovarian stimulation (OS) in therapeutic donor sperm insemination (TDI) cycles. METHODS: Retrospective cohort study between January 2011 and June 2014 at a University-affiliated private IVF clinic in Montreal, Canada. 257 normo-ovulatory women ≤40 years of age with no history of infertility undergoing 590 TDI cycles in the absence of a male partner (single women and same-sex couples) or azoospermia were included. Patients received 100 mg CC daily (145 women, 321 cycles) or letrozole 5 mg daily (112 women, 269 cycles), from days 3 to 7. Only the first 3 cycles were included per patient. Our main outcome measure was cumulative live birth rates (LBR). RESULTS: Baseline characteristics were comparable between the 2 groups. There were no differences in LBR per cycle (16.5% (53/321) vs. 11.5% (31/269), p = 0.08) and cumulative LBR (36.6% (53/145) vs. 27.7% (31/112), p = 0.13), between CC and letrozole, respectively. Multiple pregnancy rate (11.6% (8/69) vs. 8.7% (4/46), p = 0.6) and miscarriage rate (21.7 vs. 21.7%, p = 1) were also comparable between CC and letrozole, respectively. CONCLUSION: In normo-ovulatory women undergoing TDI, OS with CC or letrozole resulted in similar live birth and twin pregnancy rates.

Intravenous immunoglobulin for patients with unexplained recurrent implantation failure: a 6-year single center retrospective review of clinical outcomes.

The effectiveness of intravenous immunoglobulin (IVIg) for patients with unexplained recurrent implantation failure (uRIF) remains debated. We retrospectively analysed outcomes of uRIF patients treated with IVIg compared to a separate control uRIF cohort within our center (01/2014-12/2021). Primary outcomes included live birth, miscarriage, or transfer failure. We documented IVIg side effects and maternal/fetal outcomes. Logistic regression analysis was used to assess for association of IVIg exposure with outcomes and adjust for confounders. The study included 143 patients, with a 2:1 ratio of controls to patients receiving IVIg treatment. Patient characteristics were similar between groups. There was higher live birth rate (LBR) in patients receiving IVIg (32/49; 65.3%) compared to controls (32/94; 34%); p < 0.001). When stratifying patients into moderate and severe uRIF (respectively 3-4 and [Formula: see text] 5 previous good quality blastocyst transfer failures), only patients with severe uRIF benefited from IVIg (LBR (20/29 (69%) versus 5/25 (20%) for controls, p = 0.0004). In the logistic regression analysis, IVIg was associated with higher odds of live birth (OR 3.64; 95% CI 1.78-7.67; p = 0.0004). There were no serious adverse events with IVIg. IVIg can be considered in well selected patients with [Formula: see text] 5 previous unexplained, high quality blastocyst transfer failures. A randomized controlled trial is needed to confirm these findings.

Update on preimplantation genetic testing for aneuploidy and outcomes of embryos with mosaic results.

Preimplantation genetic testing for aneuploidy (PGT-A) is used as a frequent add-on for in-vitro fertilization (IVF) to improve clinical outcomes. The purpose is to select a euploid embryo following chromosomal testing on embryo biopsies. The current practice includes comprehensive chromosome screening (CCS) technology applied on trophectoderm (TE) biopsies. Despite its widespread use, PGT-A remains a controversial topic mainly because all of the RCTs comprised only good prognosis patients with 2 or more blastocysts available; hence the results are not generalizable to all groups of patients. Furthermore, with the introduction of the highly-sensitive platforms into clinical practice (i.e. next-generation sequencing [NGS]), a result consistent with intermediate copy number surfaced and is termed "Mosaic," consistent with a mixture of euploid and aneuploid cells within the biopsy sample. The optimal disposition and management of embryos with mosaic results is still an open question, as many 'mosaics' generated healthy live births with no identifiable congenital anomalies. The present article provides a complete and comprehensive up-to-date review on PGT-A. It discusses in detail the findings of all the published RCTs on PGT-A with CCS, comments on the subject of "mosaicism" and its current management, and describes the latest technique of non-invasive PGT-A.

Intravenous immunoglobulin use in patients with unexplained recurrent pregnancy loss.

PROBLEM: Recurrent pregnancy loss (RPL) affects up to 4% of couples attempting to conceive. RPL is unexplained in over 50% of cases and no effective treatments exist. Due to the immune system's pivotal role during implantation and pregnancy, immune-mediated RPL may be suspected and immunomodulatory treatments like intravenous immunoglobulin (IVIg) have been administered but remain controversial. The goal of our study was to evaluate our center's 6 year-outcomes and to develop a framework for IVIg use in RPL. METHOD OF THE STUDY: Retrospective, single-center cohort study. All patients having received IVIg for unexplained RPL at the McGill Reproductive Immunology Clinic (MRIC) from January 2014 to December 2020 were included if maternal age was <42 years, body mass index (BMI) < 35 kg/m2 , non-smoker and having had ≥3 consecutive RPL despite previous treatment with aspirin and progesterone. IVIg 0.6-0.8 g/kg was given prior to conception and monthly during pregnancy until 16-20 weeks' gestation. We compared IVIg treated patient's outcomes to a separate "natural history cohort". This cohort was composed of patients consulting at the McGill recurrent pregnancy loss clinic and the MRIC over a 2-year period (January 2020 to December 2021) with similar inclusion criteria as the treatment cohort but did not receive IVIg or other immunomodulatory treatments. The association of IVIg with outcomes (compared to no IVIg) was evaluated among the groups of patients with primary RPL and secondary RPL. The primary outcome was live birth rate (LBR), secondary outcomes included IVIg safety, obstetrical, and neonatal complications. RESULTS: Among 169 patients with unexplained RPL that were included in the study, 111 had primary RPL (38 exposed to IVIg and 83 controls) and 58 had secondary RPL (nine exposed to IVIG and 49 controls). Among patients with primary RPL (n = 111), the LBR was 64.3% (18/28) among patient exposed to IVIg compared to 43.4% (36/83) in controls (p = 0.079); regression analysis adjusting for BMI and number of previous miscarriages showed benefit favoring the use of IVIg (OR = 3.27, CI 95% (1.15-10.2), p = 0.03) when evaluating for live birth. In the subgroup of patients with ≥5 previous RPL and primary RPL (n = 31), IVIg was associated with higher LBR compared to control (10/15 (66.7%) vs. 3/16 (18.8%); p = 0.0113) but not the in the sub-group of patients with <5 miscarriages and primary RPL (8/13 (61.5%) vs. 33/67 (49.3%); p = 0.548). IVIG treatment did not improve LBR in patients with secondary RPL in our study (3/9 (33.3%) vs. 23/49 (47%); p = 0.495). There were no serious adverse events in the IVIg treatment group, obstetrical/neonatal complications were similar between groups. CONCLUSION: IVIg may be an effective treatment for patients with RPL if appropriately used in specific groups of patients. IVIg is a blood product and subject to shortages especially with unrestricted off-label use. We propose considering IVIg in well-selected patients with high order RPL who have failed standard medical therapy. Further mechanistic studies are needed to understand immune-mediated RPL and IVIg's mode of action. This will enable further refinement of treatment criteria and the development of standardized protocol for its use in RPL.

A 38 h interval between hCG priming and oocyte retrieval increases in vivo and in vitro oocyte maturation rate in programmed IVM cycles.

BACKGROUND: Our aim was to evaluate whether extending the interval between human chorionic gonadotrophin (hCG) priming and immature oocyte retrieval increases the oocyte maturation rate following in vitro maturation (IVM). METHODS: This study was performed retrospectively. IVM was performed on 113 polycystic ovary syndrome patients (n = 120 cycles). Oocyte collection was performed either 35 h (Group 1; n = 76) or 38 h (Group 2; n = 44) after 10,000 IU of hCG priming. Following oocyte retrieval, oocyte maturity was assessed and the remaining immature oocytes were cultured in IVM medium up to Day 2. RESULTS: The number of in vivo matured oocytes collected was significantly higher in Group 2 (13.6%, 114/840 versus 7.3%, 96/1312 in Group 1) (P < 0.01); the oocyte maturation rate after Day 1 was significantly higher (P < 0.01) in Group 2 (46.3 versus 36.0% in Group 1); and clinical pregnancy (40.9 versus 25%) and implantation rates (15.6 versus 9.6%) were better in Group 2 than those in Group 1. CONCLUSIONS: The results suggest that extending the period of hCG priming time from 35 to 38 h for immature oocyte retrieval promotes oocyte maturation in vivo and increases the IVM rate of immature oocytes. Therefore, oocyte retrieval after 38 h of hCG priming may improve subsequent pregnancy outcome in cycles programmed for IVM treatment.

Comparison of in-vitro maturation cycles with and without in-vivo matured oocytes retrieved.

This study compared the embryological characteristics and clinical outcome of in-vitro maturation (IVM) treatment cycles with and without in-vivo matured oocytes collected following human chorionic gonadotrophin (HCG) priming. The patients were administered 10,000 IU of HCG subcutaneously when endometrial thickness reached > or =6 mm and oocyte collection was performed 35-36 h after HCG administration. The clinical outcome and embryological aspects were analysed between IVM cycles with (group 1) and without (group 2) in-vivo matured oocytes. In group 1, three (range 1-12) in-vivo matured oocytes per patient were retrieved on average. The number of good quality embryos derived from in-vivo matured oocytes in group 1 was significantly higher than those derived from in-vitro matured oocytes in group 1 and group 2 (P < 0.05). However, there was no difference between the number of good quality embryos produced from in-vitro matured oocytes in the two groups. There were 12 clinical pregnancies (40.0%) in group 1, and seven pregnancies (23.3%) in group 2. These results suggest that IVM cycles with in-vivo matured oocytes resulted in a good clinical pregnancy rate, which could be explained by the superior quality of embryos derived from the in-vivo matured oocytes.

Ectopic pregnancy after bilateral salpingectomy.

Ectopic pregnancy is a life threatening condition and is a major event in a woman's reproductive life. We report herein an unusual case of repeated ectopic pregnancy even after the excision of both fallopian tubes with a deleterious consequences and a near miss. This case teaches us a lesson not to forget ectopic pregnancy. The lady in this report underwent in vitro fertilization treatment cycle due to absence of both fallopian tubes as consequence of previous ectopic pregnancy and a hydrosalpinx; she conceived successfully but unfortunately the pregnancy was another ectopic pregnancy.

Chronic endometritis in women with recurrent pregnancy loss and recurrent implantation failure: prevalence and role of office hysteroscopy and immunohistochemistry in diagnosis.

OBJECTIVE: To determine the prevalence of chronic endometritis (CE) in patients with recurrent implantation failure (RIF) after IVF and unexplained recurrent pregnancy loss (RPL). DESIGN: Prospective observational study between November 2012 and March 2015. SETTING: University-affiliated private IVF clinic. PATIENT(S): Women with RIF after IVF (group 1) and unexplained RPL (group 2). INTERVENTION(S): Office hysteroscopy followed by an endometrial biopsy was performed as part of the workup for RIF and RPL. The diagnosis of CE was histologically confirmed using immunohistochemistry stains for syndecan-1 (CD138). MAIN OUTCOME MEASURE(S): The prevalence of CE in each group and the sensitivity/specificity of office hysteroscopy in the diagnosis of CE. RESULT(S): Ninety-nine patients were included (46 in group 1 and 53 in group 2). The mean age was 36.3 ± 4.9 years in group 1 and 34.5 ± 4.9 years in group 2. Five biopsies were uninterpretable (three in group 1 and two in group 2) because of insufficient specimen. The prevalence of CE was 14% (6/43) in group 1 and 27% (14/51) in group 2. The sensitivity and specificity of office hysteroscopy in the diagnosis of CE were 40% (8/20) and 80% (59/74), respectively. CONCLUSION(S): We found a high prevalence of immunohistochemically confirmed CE in women with RIF and RPL. Office hysteroscopy is a useful diagnostic tool but should be complemented by an endometrial biopsy for the diagnosis of CE. CLINICAL TRIAL REGISTRATION NO: NCT01762098.

450 IU versus 600 IU gonadotropin for controlled ovarian stimulation in poor responders: a randomized controlled trial.

OBJECTIVE: To compare the outcomes of controlled ovarian stimulation/in vitro fertilization cycles using 450 IU and 600 IU gonadotropin per day in women at risk of poor ovarian response. DESIGN: Prospective randomized controlled nonblinded study. SETTING: University-affiliated private IVF center. PATIENT(S): Women considered to be at risk of poor ovarian response: aged <41 years with basal FSH >10 IU/L, antimüllerian hormone <1 ng/mL, antral follicle count ≤ 8, or a previous IVF cycle with ≥ 300 IU/d gonadotropin that resulted in a cancellation, <8 follicles, or <5 oocytes. INTERVENTION(S): A total of 356 patients underwent a microdose GnRH agonist flare-up IVF/intracytoplasmic sperm injection protocol with a fixed daily dose of either 450 IU FSH (n = 176) or 600 IU FSH (n = 180) equally divided between Menopur and Bravelle. MAIN OUTCOME MEASURE(S): Number of mature oocytes retrieved. RESULT(S): The two groups were similar in terms of age, ovarian reserve, cause of infertility, duration of stimulation, and cycle cancellation rate. There were no significant differences in the number of metaphase II oocytes retrieved (4 [range 0-6] vs. 4 [range 2-7]), fertilization rate (62.4% vs. 57.0%), biochemical pregnancy rate (20.5% vs. 22.9%), clinical pregnancy rate (16.4% vs. 18.3%), and implantation rate (29.8% vs. 30.4%) between the 450 IU and 600 IU groups, respectively. CONCLUSION(S): Gonadotropin of 600 IU/d does not improve outcome of IVF cycles compared with 450 IU/d in women at risk of poor ovarian response. CLINICAL TRIAL REGISTRATION NUMBER: NCT00971152.

A prospective study to evaluate the efficacy of two- and three-dimensional sonohysterography in women with intrauterine lesions.

OBJECTIVE: To measure the accuracy of three-dimensional (3D) sonohysterography in detecting intrauterine lesions. DESIGN: Prospective study. SETTING: Teaching hospital. PATIENT(S): Two hundred nine infertile patients suspected to have an intrauterine lesion on 2D ultrasound or hysterosalpingography. INTERVENTION(S): Three-dimensional ultrasound, 2D and 3D sonohysterography (SHG). Ninety-two of the patients had a lesion distorting the endometrium on the 3D SHG, and those were referred for hysteroscopy. MAIN OUTCOME MEASURE(S): Sensitivity and specificity of 2D, 3D ultrasound, and 2D SHG compared to 3D SHG. RESULT(S): Of the 92 patients with a lesion, 48 had polyps, 35 submucous/intramural myomas, 3 both polyps and myomas, 4 müllerian anomalies, 1 thick endometrium, and 1 synechiae. Compared with the 3D SHG results, the sensitivity and specificity were 97% and 11% for the 2D transvaginal ultrasound, 87% and 45% for the 3D ultrasound, and 98% and 100% for the 2D SHG. In the group of 59 patients who had hysteroscopy, the sensitivity of the 2D SHG and 3D SHG were 98% and 100%, with a positive predictive value of 95% and 92%, respectively. CONCLUSION(S): Three-dimensional sonohysterography allows precise recognition and localization of lesions. If 2D and 3D SHG are normal, invasive diagnostic procedures such as hysteroscopy could be avoided.

Natural-cycle in vitro fertilization combined with in vitro maturation of immature oocytes is a potential approach in infertility treatment.

OBJECTIVE: To describe pregnancies and live births that resulted from IVF of mature oocytes retrieved from dominant follicles in a natural cycle combined with in vitro maturation (IVM) of immature oocytes retrieved from small follicles. DESIGN: Case reports. SETTING: McGill Reproductive Center, Royal Victoria Hospital, McGill University. PATIENT(S): Three women with normal ovaries or polycystic ovaries who underwent infertility treatment. INTERVENTION(S): Administration of s.c. hCG (10,000 IU) 36 hours before oocyte retrieval in a natural cycle. After aspiration of all follicles, mature oocytes were inseminated immediately; immature oocytes were matured in vitro, inseminated by intracytoplasmic sperm injection (ICSI), and then the embryos transferred. MAIN OUTCOME MEASURE(S): Pregnancy and live birth. RESULT(S): Three pregnancies (two live births and one ongoing at time of writing) were achieved after the combination of natural-cycle IVF with IVM after transfer of the resulting embryos. CONCLUSION(S): Natural-cycle IVF combined with IVM might be a new approach to IVF treatment for women with various causes of infertility.

Comparison of daily and alternate day recombinant follicle-stimulating hormone stimulation protocols for intrauterine insemination.

OBJECTIVE: To determine the efficacy of daily versus alternate-day stimulation for patients undergoing intrauterine insemination (IUI). DESIGN: Retrospective comparative study. SETTING: University tertiary care center for infertility. PATIENT(S): Women with anovulatory or unexplained infertility for over 12 months who had not responded to or not conceived with clomiphene citrate treatment. INTERVENTION(S): Ovarian stimulation with recombinant follicle-stimulating hormone (FSH; follitropin-beta) given either daily or on alternate days before IUI. MAIN OUTCOME MEASURE(S): Clinical pregnancy at ultrasound 4 weeks after IUI. Secondary outcome measures were duration of stimulation, total gonadotropin dose, ovarian response, and multiple pregnancy rate. RESULT(S): Of the 212 women who underwent a first cycle of gonadotropin stimulation, 28 had daily injections and 117 had alternate-day injections of follitropin-beta only for IUI. Female age, antral follicle count, and day-3 serum FSH were comparable. The median duration of stimulation (8 days vs. 8 days) and the median number of follicles over 14 mm (3.5 vs. 3.0) were similar in both groups. However, the total recominbinant FSH dose (825 vs. 625 IU) and endometrial thickness (10.1 vs. 9.3 mm) were greater in the daily injection group. The clinical pregnancy rate per cycle was 42% (12 out of 28) in the daily injection group and 19% (22 out of 117) in the alternate-day group. CONCLUSION(S): Daily recombinant FSH stimulation for IUI seems to be associated with a higher clinical pregnancy rate than alternate-day FSH stimulation. Prospective randomized trials would be needed to determine whether this is indeed the case.

Pregnancy loss in pregnancies conceived after in vitro oocyte maturation, conventional in vitro fertilization, and intracytoplasmic sperm injection.

OBJECTIVE: To compare rates of pregnancy loss after oocyte maturation in vitro (IVM), after IVF, and after intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective comparative study. SETTING: University tertiary-care center for infertility. PATIENT(S): Women undergoing assisted reproductive technology in a single center. INTERVENTION(S): Oocyte maturation in vitro, IVF, or ICSI, as indicated. MAIN OUTCOME MEASURE(S): Biochemical pregnancy, clinical miscarriage, ectopic pregnancy, and late fetal loss. RESULT(S): There were 1,581 positive pregnancy tests (120 IVM, 849 IVF, and 612 ICSI). The biochemical pregnancy loss rate did not statistically significantly differ among the groups: 17.5% (21/120) after IVM, 17.0% (144/849) after IVF, and 18.0% (110/612) after ICSI. The clinical miscarriage rate after IVM was 25.3% (25/99), which was statistically significantly different compared with 15.7% (111/705) after IVF and 12.6% (63/502) after ICSI. However, the clinical miscarriage rates in women with polycystic ovary syndrome were statistically similar, at 24.5% (24/98) after IVM and 22.2% (18/81) after IVF. The ectopic pregnancy rates also were statistically similar: 1.0% (1/99) after IVM, 2.3% (16/705) after IVF, and 1.8% (9/502) after ICSI. The late fetal loss rates were similar as well: 1.0% (1/99) after IVM, 2.7% (19/705) after IVF, and 2.9% (14/502) after ICSI. There were no chromosomal abnormalities in the IVM group. CONCLUSION(S): There is a higher rate of clinical miscarriage after IVM when compared with IVF and ICSI. This appears to be related to polycystic ovary syndrome rather than to the IVM procedure.

Repeated pregnancies and live births after in vitro maturation treatment.

OBJECTIVE: To discuss and describe the successful treatment of women with primary infertility using in vitro maturation (IVM) of immature human oocytes resulting in repeated pregnancies and live births in the same individuals. DESIGN: Case report. SETTING: McGill Reproductive Center, Royal Victoria Hospital, McGill University. PATIENT(S): Six patients who underwent IVM treatment. INTERVENTION(S): In vitro maturation and fertilization of immature human oocytes. MAIN OUTCOME MEASURE(S): Clinical pregnancies and live births. RESULT(S): We report 11 singleton and 2 twin live births as a result of IVM treatment in six women with polycystic ovary syndrome. CONCLUSION(S): In vitro maturation of human oocytes is a novel treatment in the management of infertility. It is an effective method of conception, especially in women who have polycyctic ovaries.