Hope for male fecundity: clinically insignificant changes in semen parameters over 10 years at a single clinic while assessing an infertility population.

PURPOSE: What is the trend in sperm parameters in a group of men attending a single reproductive center, over a 10-year period? METHODS: A retrospective study was conducted on 12,188 semen samples obtained from unique individuals who attended a university reproductive clinic from 2009 to 2018, inclusively. Semen analysis was done using computer-assisted sperm analysis and verified by an andrologist. Analysis was done after dividing the dataset into two groups: above WHO 2010 lower reference limits (ARL) (N = 6325) and below the reference limits (BRL) (N = 5521). RESULTS: Volume increased slightly (ARL, p = 0.049) before returning to baseline or was stable (BRL, p = 0.59). Sperm concentration and total count of the BRL and ARL group declined initially and then recovered slightly (p < 0.0001, in all cases). Although these changes were statistically significant, this was due to the large study population; clinically, these changes were quite mild and would not have been significant for fertility. Sperm total motility and progressive motility of both the BRL group and the ARL group increased slightly from 2009 until 2015 and then decreased back to baseline (p < 0.0001). This change offset the decrease in count seen in those years. A spurious change was observed with sperm morphology that declined after the first 2 years and remained stable thereafter (p < 0.0001, in both groups). However, this change was attributed to a contemporaneous change in the method of analyzing strict morphology which happened when the change occurred. CONCLUSION: While statistically significant changes were found, clinically, these changes were quite mild and would not have been significant for fertility.

Effects of cancer stage and grade on fertility preservation outcome and ovarian stimulation response.

STUDY QUESTION: Do the stage and grade of malignancy affect the fertility preservation outcome in females? SUMMARY ANSWER: Patients with high-grade cancer have a decreased number of retrieved mature oocytes and cryopreserved embryos. WHAT IS KNOWN ALREADY: Cancer has local and systemic effects on the host. The effects of cancer spread and aggressiveness on the ovarian function and stimulation response remain unclear. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study evaluating data of all fertility preservation treatment cycles among women with cancer at the reproductive unit of the McGill University Health Centre in the period from 2008 to 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Study inclusion criteria were age 18-38 years, first stimulation cycle, GnRH-antagonist protocol and early follicular phase stimulation start. Only one stimulation cycle per patient was included. Patients with ovarian pathology, previous ovarian surgery and previous chemo- or radiotherapy were excluded. The outcomes of women with low-stage cancer (local tumor Stage I-II, no lymph node involvement, no metastases) were compared with those with high-stage disease (local tumor Stage III-IV, lymph node involvement or metastases). Similarly we compared those with low-grade (G1-2) and high-grade (G3-4) malignancies. The primary outcome measure was the number of mature oocytes retrieved. The secondary outcomes included the total number of retrieved oocytes, the number of vitrified oocytes, and the number of frozen embryos. We used Student's t-test for normally distributed data and Wilcoxon test for skewed data. To determine factors associated with good fertility preservation outcome defined as over 10 retrieved mature oocytes, we used multivariate logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 147 patients were included in the final analysis. Age, body mass index, ovarian reserve parameters of the study groups in stage- and grade-based analyses were similar. Compared to women with low-stage cancer (n = 83), those with high-stage cancer (n = 64) required a higher dose of gonadotropin (P = 0.02). The number of retrieved mature oocytes (9 (7-13) versus 8 (5-12); P = 0.37) and vitrified oocytes (10 (7-15) versus 10 (7-13); P = 0.53) were similar between the two groups. However, in cycles where fertilization of all retrieved oocytes was performed, the fertilization rate (82.7% versus 71.5%; P = 0.03) and the number of vitrified embryos (6.2 ± 3.2 versus 4.3 ± 2.1; P = 0.01) were higher in the low-stage group. Compared to patients with low-grade cancer (n = 62), those with high-grade disease (n = 85) had significantly lower number of retrieved mature oocytes (11 (7-15) versus 8 (5-11); P = 0.002) and vitrified oocytes (12 (8-15) versus 10 (7-11); P = 0.005). The number of vitrified embryos was lower in high-grade group (6.5 ± 3.5 versus 4.6 ± 2.3; P = 0.03) in cycles where the fertilization was performed. In multivariate logistical analysis, the low-grade cancer was significantly associated with retrieval of over 10 mature oocytes (OR = 4.26; 95% CI 1.82-9.98; P = 0.0009). LIMITATIONS, REASONS FOR CAUTION: The main limitations of the study include its retrospective design and the relatively small sample size in the embryological outcome analysis. The results of our study should be viewed with caution as different malignancy types were included in the study groups, although their distribution between the study groups was similar. WIDER IMPLICATIONS OF THE FINDINGS: Cancer grade seems to have a negative impact on the fertility preservation outcome and the ovarian stimulation response. STUDY FUNDING/COMPETING INTEREST(S): Authors have not received any funding to support this study. There are no conflicts of interest to declare.

Prevalence, clinical characteristics, and reproductive outcomes of polycystic ovary syndrome in older women referred for tertiary fertility care.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age women. The clinical symptoms of PCOS vary with female age, as older women tend to have lower hyperandrogenic symptoms and many regain regular cycles. In this study, we aimed to estimate the prevalence of PCOS among older women referred for fertility care, describe their clinical characteristics, and compare their reproductive outcomes to those of matched control group. METHODS: A retrospective study conducted at a single reproductive center. All women aged ≥ 40, who were referred for in-vitro fertilization (IVF), between the years 2011-2015 were screened for possible inclusion. The PCOS diagnosis (was) made based on the Rotterdam criteria. The reproductive outcomes of the PCOS group were compared to those of matched control with tubal infertility. RESULTS: During the study period, 1427 women, aged 40 years and over, underwent a total of 2124 IVF cycles. Of these, 72 (5%) women were diagnosed with PCOS. In 69 (95.6%), the PCOS diagnosis was made by a combination of polycystic ovary morphology (PCOM) and anovulation. Compared to women with tubal factor infertility, women with PCOS needed lower doses of gonadotropins, had higher number of retrieved oocytes (16.6 vs. 10.4) and higher number of cycles with embryo cryopreservation (47 vs. 22.9%). This resulted in higher cumulative live birth in the PCOS group (26.3 vs. 15.2%, p = 0.04). CONCLUSION: PCOS comprised 5% of the infertility diagnosis in women aged ≥ 40; PCOM and anovulation were the most prominent features. The higher oocyte number resulted in improved cumulative live birth rate.

Predictive factors for live birth after in vitro maturation of oocytes in women with polycystic ovary syndrome.

OBJECTIVE: In vitro maturation (IVM) of human oocytes can be an alternative treatment option to conventional in vitro fertilization. Women with polycystic ovary syndrome (PCOS) are considered the classical candidates for IVM because of the associated ovarian morphology and because IVM diminishes the risk of developing ovarian hyperstimulation syndrome. The objective of this study was to identify predictive factors for live birth in a cohort of women with PCOS who underwent IVM. METHODS: This retrospective study included 159 patients with PCOS who had IVM cycles in which single or double embryo transfer was performed. The IVM protocol included three days of gonadotropin ovarian stimulation and hCG priming when the leading follicle size was 10-12 mm. Collected cumulus-oocyte complexes were cultured for 24 h for maturation. Intracytoplasmic sperm injection (ICSI) was used for fertilization. Embryo transfer was performed two days after fertilization. Demographic and clinical parameters were analyzed with logistic regression to identify predictors for live birth. RESULTS: The women's mean age was 27.4 years, the mean number of retrieved oocytes was 14, and the live birth rate was 34.6%. The logistic regression revealed the following significant factors for live birth: infertility duration (OR 0.9; 95% CI, 0.82-0.98), number of collected oocytes (OR 1.56; 95% CI, 1.01-3.2), embryo cell number (OR 2.1; 95% CI, 1.4-3.5), and embryo grade (OR 1.84; 95% CI, 1.13-4.2). CONCLUSION: Infertility duration, oocyte number, embryo cell number, and embryo grade were the most significant predictors for live birth after IVM in PCOS patients. These prognostic factors can be used when planning treatment or counselling patients.

The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age.

STUDY QUESTION: Does ICSI improve reproductive outcomes compared with conventional IVF when used for non-male factor infertility in women aged 40 years and over? SUMMARY ANSWER: There is no advantage of ICSI over conventional IVF in women aged 40 years and over when used for non-male factor infertility. WHAT IS KNOWN ALREADY: The use of ICSI has increased dramatically in recent years and is being applied for indications other than male factor infertility. Currently, ICSI is used in 65% of IVF cycles in Europe and in 76% of cycles in the USA. Despite its increase use, there is no clear evidence of a benefit in using ICSI over conventional IVF. Older women undergoing infertility treatments are at an increased risk of having diminished ovarian reserve and lower oocyte quality, which could make ICSI the preferred insemination method in this group. However, studies that have examined the benefits of ICSI in this age group are lacking. STUDY DESIGN, SIZE, DURATION: A retrospective, single center study included women, aged 40-43 years, who underwent IVF treatments for non-male factor infertility between January 2012 until June 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 745 women were included in the study. Of these, 490 women underwent ICSI and 255 women underwent conventional IVF. In order to be included in the study, women had to be at least 40 years of age at the beginning of ovarian stimulation and their male partner had to have normal sperm parameters according to World Health Organisation (WHO) fifth edition. Exclusion criteria included: more than three previous IVF cycles, a history of fertilization failure or low fertilization (<50%), the use of donor or frozen oocytes and the use of donor or frozen sperm samples. The primary outcome was the live birth rate. Secondary outcomes included fertilization rates, fertilization failure and embryo quality. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics were similar between the two groups, except for the number of previous IVF cycles, which was higher in the ICSI group (1.0 vs. 0.6, P = 0.0001). Despite similar numbers of oocytes retrieved (7.2 vs. 6.5), when examining oocytes maturity (performed 2 h after oocyte retrieval in the ICSI group and after 18 h in the conventional IVF group), the conventional IVF group had a higher number of Metaphase II (MII) oocytes (6.1 vs. 4.7, P < 0.0001). The conventional IVF group also had higher numbers of zygotes formed (4.48 vs. 3.66, P = 0.001), more cycles with embryos transferred at the blastocyst stage (36 vs. 26%, P = 0.005) and more cycles where embryos were available for cryopreservation (26.4 vs. 19.7%, P = 0.048), compared with the ICSI group. The fertilization rates (64 vs. 67%) and fertilization failure (9.0 vs. 9.7%) were similar. After logistic regression analysis controlling for confounders, the live birth rates were similar between the groups (11.9 vs. 9.6%). Subgroup analyses of women undergoing their first IVF cycle and women with ≤3 oocytes retrieved did not show an advantage of ICSI over conventional IVF. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of this study was a major limitation. The ICSI group had a higher number of previous IVF cycles, which could mean that ICSI was performed in poorer prognosis patients. Moreover, although this study is one of the largest studies to examine the question of whether ICSI is of value for older women with non-male factor infertility, based on a post hoc power analysis, it was still underpowered to detect differences in live birth rates, which can limit the conclusions of the study. Prospective studies are needed to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS: The decision regarding performing ICSI should be based on sperm parameters and previous history. The use of ICSI for the sole indication of advanced maternal age shows no benefit over conventional IVF. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: N/A.

Cumulative live birth rate following elective single blastocyst transfer compared with double blastocyst transfer in women aged 40 years and over.

This retrospective cohort study aimed to identify predictive factors for live birth following blastocyst transfer in women aged 40-43, and to compare the cumulative live birth rate (LBR) following elective single blastocyst (eSBT) and double blastocyst (DBT) transfer. The study included 411 women who had fresh blastocyst transfers on day 5. In stepwise logistic regression, independent predictive factors for live birth were: transferring fully expanded blastocysts (Gardner stage ≥3) (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.59-9.71) and transferring two blastocysts compared with a single blastocyst (OR 1.7, 95% CI 1.08-2.9). Maternal age was not found to be significant (OR 0.78, 95% CI 0.62-1.1). When comparing eSBT (n = 150) with DBT (n = 151), the DBT group achieved higher LBRs (26.5 versus 19.3%, P = 0.017) and higher multiple births (0 versus 17.5%, P = 0.02). However, the cumulative LBR was similar (28.0 versus 31.1%), with significantly lower multiple births in the eSBT group (0 versus 14.9%, P = 0.03). These results indicate that in women aged 40-43, when fully expanded blastocysts are achieved, maternal age is not a predictor for live birth, and eSBT can be performed without compromising cumulative LBRs.

Elective single blastocyst transfer in advanced maternal age.

PURPOSE: The purpose of this study was to investigate reproductive outcomes following elective single blastocyst transfer (eSBT) compared with those of double blastocyst transfer (DBT) in advanced maternal age. METHODS: This was a retrospective cohort study performed at an academic fertility center. All women aged 40 and over for whom in vitro fertilization (IVF) cycles were performed and in whom embryo culture was extended to the blastocyst stage were reviewed for possible inclusion. Exclusion criteria included the following: women with >3 previous IVF cycles, the use of donor or frozen oocytes, preimplantation genetic diagnosis/preimplantation genetic screening cycles, and cycles in which embryos did not reach the blastocyst stage on day 5. The study included 310 women; 148 were included in the eSBT group and 162 were included in the DBT group. Live birth rate (LBR) was the main outcome. Outcomes were analyzed using logistic regression, controlling for confounders. These confounders were embryo expansion, embryo quality, and the number of previous IVF cycles. RESULTS: The mean age of the whole group was 41 ± 0.91 years, and the LBR was 21.6%. The eSBT group and the DBT group achieved similar clinical pregnancy rates (33 vs. 33%) (OR 1.04; 95%CI, 0.62-1.75) and LBRs (20 vs. 22.8%) (OR 1.43; 95% CI, 0.78-2.64). The multiple birth rate was lower in the eSBT group (0 vs. 16%, p = 0.02). The subgroup of women who had elective DBT (eDBT) achieved a higher LBR (20 vs. 30.6%) (OR 2.32; 95% CI, 1.16-4.68) and a higher multiple birth rate (0 vs. 22%, p = 0.001). Cycles with early blastocyst transfers were associated with lower LBRs compared with cycles with fully expanded blastocyst transfers (11 vs. 24%, p = 0.02). CONCLUSION: The results of this study indicate that eSBT is associated with similar LBRs compared to the entire DBT cohort; however, when supernumerary blastocysts are available for cryopreservation, eDBT is associated with both higher LBRs and a higher number of multiple births. Studies assessing the cumulative LBR in advanced maternal age after single blastocyst transfer and subsequent frozen-thawed blastocyst transfers are needed.

Inconsistencies between endometrial receptivity assay and Adhesio-RT test for the window of implantation in women with repetitive failed donor oocyte embryo transfers.

Two commercially available second-generation endometrial receptivity assays using microarray analysis or next-generation sequencing are available in the market: endometrial receptivity assay (ERA) (Igenomix Laboratories) and Adhesio RT (OVO laboratories, Montreal, Canada). Little is known about how the results of these tests compare. We present a case of a subject with repetitive failed donor oocyte embryo transfer, who underwent evaluation of endometrial receptivity using both the Adhesio and ERA tests. These two tests did not provide consistent results, with ERA suggesting receptivity on day 5 of progesterone treatment and Adhesio suggesting receptivity on the eighth day. An ERA test subsequently performed on the eighth day of progesterone treatment was suggestive of post-receptive endometrium during the same time frame that Adhesio was suggestive of receptive endometrium. In conclusion, it is important to note that these two tests may not provide consistent results in at least some subjects. Therefore, intertest validity studies are recommended.

Does the timing of cabergoline administration impact rates of ovarian hyperstimulation syndrome?

OBJECTIVE: Does the timing of cabergoline administration impact the rate of mild/moderate ovarian hyperstimulation syndrome in women with a GnRH agonist trigger? METHODS: We conducted a retrospective cohort analysis of 285 in-vitro fertilization patients at risk of OHSS who received a GnRH agonist trigger from 2011 to 2019 at McGill University Health Centre. Group 1 (Trig, n=101) began taking cabergoline 0.5 mg orally for 7 days at the time of GnRH agonist trigger, while Group 2 (Retriev, n=184) started taking cabergoline on the day of oocyte retrieval. The rates of OHSS were then compared between the groups using analysis of variance and chi-square analysis, where appropriate. RESULTS: The baseline demographic characteristics of the two groups were similar. Trig appeared to be at a slightly higher risk of OHSS based on a significantly higher antral follicle count (20.2±4.2 vs. 19.0±4.3; P=0.02), higher number of stimulated follicles >10 mm at trigger (25.7±7.0 vs. 22.8±8.3, P=0.003), and higher peak serum E2 level (17,325±2,542 vs. 14,822±3,098; P=0.0001). The Trig group had lower rates of mild and moderate OHSS (24% vs. 36%; P=0.045). Neither group had any patients who developed severe OHSS. Trig had fewer patients presenting with pelvic free fluid (13% vs. 23%; P=0.03), lower hematocrit (37.8±4.8% vs. 40.5±4.2%; P=0.0001), higher albumin concentrations (30.4±2.7 vs. 29.5±2.0; P=0.01), and lower potassium concentrations (3.9±0.5 vs. 4.2±0.7; P=0.0002). CONCLUSION: Cabergoline at the time of trigger as compared to the time of collection should be investigated to assess its role in reducing the rates of mild/moderate OHSS.

The use of in vitro maturation in stimulated antagonist in vitro fertilization cycles of normo-hyperresponder women due to arrested follicular development: A rescue procedure.

Objective: To evaluate the impact of rescue in vitro maturation (IVM) on the clinical outcomes of women with arrested follicular development in stimulated in vitro fertilization (IVF) cycles. Materials and Methods: This is a retrospective review of 13 patients who were evaluated as normo-hyperresponders for ovarian stimulation. The main outcome measure was the clinical pregnancy and livebirth rates. The purpose of gonadotropin stimulation in patients undergoing IVF is to retrieve multiple oocytes by avoiding multifetal gestation and Ovarian Hyperstimulation syndrome (OHSS). The ovarian response to stimulation ranges from poor response to OHSS, which is related to the follicular number and the dose of the gonadotropins used. However, in some cycles of normo-hyperresponder women, follicular development decelerates or ceases. Close follow-up in a daily manner and increasing the dose of gonadotropins did not change the follicular arrest. This clinical situation has two edges; one is cycle cancellation, which has undesired psychological outcomes for women and the IVF team, and second one is the prolongation of the IVF cycle. For such circumstances, IVM may be a valuable option. Stimulated IVF cycles were converted to IVM as a rescue IVM procedure following detailed informed consent of the women who were close to cycle cancellation. Results: Thirteen 13 IVM cycles and their clinical outcomes are presented. Six women achieved pregnancies, but only 4 delivered 5 healthy live born. The other two women had biochemical loss during follow-up. Conclusion: Based on the data obtained, it can be concluded that gonadotropin-stimulated cycles with follicular arrest at the edge of cancellation can be shifted to rescue IVM procedures with reasonable clinical outcomes.

Oocyte in vitro maturation: A sytematic review.

In vitro maturation (IVM) is one of the most controversial aspects of assisted reproductive technology. Although it has been studied extensively, it is still not a conventional treatment option and is accepted as an alternative treatment. However, studies have shown that IVM can be used in almost all areas where in vitro fertilization (IVF) is used and it has a strong place in fertility protection and Ovarian Hyperstimulation syndrome management. The aim of this systematic review was to address all aspects of the current knowledge of IVM treatment together with the evolution of IVM and IVF.

Reproductive outcomes after a single dose of gonadotropin-releasing hormone agonist compared with human chorionic gonadotropin for the induction of final oocyte maturation in hyper-responder women aged 35-40 years.

OBJECTIVE: To investigate the reproductive outcomes after the use of GnRH agonist (GnRHa) compared with hCG for the induction of final oocyte maturation in GnRH antagonist cycles performed in hyper-responder women aged 35-40 years. DESIGN: Retrospective study. SETTING: Academic fertility center. PATIENT(S): Two hundred seventy-two hyper-responder women aged 35-40 years who underwent controlled ovarian stimulation under GnRH antagonist suppression were included. Final oocyte maturation was performed with GnRHa (n = 168) or hCG (n = 104). Embryos were cryopreserved at the blastocyst stage and transferred in subsequent warming cycles (n = 542). Subjects were included in the analysis until live birth was achieved, after which they were excluded from further analysis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cumulative live birth rate. RESULT(S): Subjects in the GnRHa group achieved a higher number of oocytes (22 vs. 21) and a higher number of mature oocytes (16 vs. 14). The number of cryopreserved blastocysts (median of five blastocysts in both groups) was similar. Women in the hCG group needed a lower number of warming cycles to achieve live birth (1.32 vs. 2.12), had higher embryo implantation rates (48% vs. 39%), and the proportion of embryos transferred until live birth was lower (33% vs. 57%). The cumulative live birth rate was similar between the groups (48.15% vs. 48%). CONCLUSION(S): Although the cumulative live birth rate is similar, a single dose of GnRHa possibly results in suboptimal oocyte and embryo competence, as manifested by decreased embryo implantation rates and increased time needed to achieve live birth.

A Case of Chronic Abdominal Neuropathic Pain and Burning after Female Genital Cutting.

Introduction. Female genital cutting is prevalent in the Middle Eastern and African countries. This ritual entails not only immediate complications such as infection, pain, and haemorrhage, but also chronic ones including dysmenorrhea and dyspareunia. However, there is limited data on neuropathic pain secondary to female genital mutilation when searching the literature. Case. This case discusses a 38-year-old female with a history of infibulation who presented with a chronic burning abdominal and anterior vulvar pain including the related investigations and treatment. Discussion. This case brings to light the additional delayed complication of this ritual: sensory neuropathy. Our goal is to educate health professionals to be aware of these complications and to appropriately investigate and treat them in order to find a solution to relieve the patients' symptoms.