Measures Of Ovarian Reserve Research Articles

Z-Scores for Assessing Ovarian Reserve in Young Patients Undergoing Fertility Preservation.

Women are born with a non-renewable pool of ovarian follicles, referred to as the ovarian reserve. This reserve consists of primordial follicles in the ovaries and can be affected by many factors, such as genetic and endocrine disorders, medical interventions, and endocrine disruptors. Fertility preservation is recommended when gonadotoxic treatments are necessary. The preferred options for women are oocyte and embryo cryopreservation. However, in very young, sexually immature patients, ovarian tissue cryopreservation is the only option. Knowing the follicular density of cryopreserved tissue samples is essential in fertility counseling for young patients. This protocol demonstrates the use of Z-scores for cortical follicle density as a tool to evaluate the quality of ovarian tissue in girls and young women aged 25 years and below who are undergoing fertility preservation. Follicle density in patient samples is compared to age-normalized reference standards, developed by Hassan et al. to estimate possible deviations from the standard. The follicle density is measured through histological quantification. For this, a small piece of ovarian cortical tissue (~2 mm x 2 mm x 2 mm) is fixed in either Bouin's or formaldehyde solution, embedded in paraffin, sectioned at 4 µm thickness, stained with hematoxylin and eosin, and digitized using a slide scanner. Follicular stages present in the cortex range from primordial to primary follicles. The cortical area was 1 mm from the surface epithelium on histological sections. Follicle density is calculated using a modified formula presented by Schmidt et al., and the Z-score is determined using the reference mean and standard deviation. The Z-score indicates how much the measured value deviates from the reference mean, determiningreduced (<-1.7 Z-score) ovarian reserve. With this method, follicle densities can be used as a valuable measure of ovarian reserve for young patients requiring fertility preservation.

O-256 Evaluation of Anti-Mullerian hormone levels in reproductive age severely obese women six months after bariatric surgery

Abstract Study question Do serum levels of anti-Müllerian hormone (AMH) change in women of reproductive age following weight loss induced by bariatric surgery? Summary answer Following six months post-bariatric surgery, despite substantial weight loss, both Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy patients exhibited consistent AMH levels. What is known already Obesity negatively affects fertility, IVF outcomes, and potentially AMH) levels. AMH correlates to the number of growing follicles and is currently the best measure of ovarian reserve. Bariatric surgery (BS) has been considered as the most effective method to achieve sustainable weight loss. Many studies have demonstrated that there is an increase of spontaneous pregnancies and a reduction in complications during pregnancy or delivery post-bariatric surgery. Despite these benefits, the specific impact of BS on ovarian reserve and AMH levels remains unclear. Several studies have already considered the effects of surgery-induced weight loss on ovarian reserve, often showing conflicting results. Study design, size, duration This prospective study included 22 obese women in reproductive age with BMI ≥ 40 or ≥ 35 kg/m2 with at least one obesity-related comorbidity at baseline and 6 months after undergoing either sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB). Participants/materials, setting, methods Women aged 20–34 years with a median BMI of 41.53 kg/m² were included at baseline. Two medical consultations occurred: one preoperatively and another 6 months postoperatively. Each session included body weight and height measurements, as well as serum AMH testing using the Elecsys® AMH kit (Diagnostics Roche) and the electrochemiluminescence method - Cobas (Diagnostics Roche). Patients were divided into two groups: group 1 underwent RYGB, while group 2 underwent sleeve gastrectomy. Main results and the role of chance After six months post-bariatric surgery, all participants exhibited a significant reduction in BMI, with the median dropping from 41.53 kg/m² to 29.56 kg/m², representing a substantial 28.82% decrease (p &amp;lt; 0.001). In Group 1, the median BMI decreased from 38.51 kg/m² to 29.27 kg/m², a statistically significant reduction of 27.30% (p = 0.003). Group 2 also saw a significant drop, from 42.53 kg/m² to 30.10 kg/m², reflecting a 29.23% reduction (p = 0.003). Contrastingly, no significant changes in AMH levels were noted six months post-bariatric surgery. The median AMH level slightly decreased from 3.02 ng/mL to 2.95 ng/mL, a non-significant 2.32% reduction (p = 0.783). In Group 1, the median AMH level increased insignificantly from 2.54 ng/mL to 2.92 ng/mL, a 14.96% rise (p = 0.424). In Group 2, there was a non-significant 6.88% decrease, from 3.20 ng/mL to 2.98 ng/mL (p = 0.722). Pre-surgery, 12 patients reported regular menstrual cycles, while 10 reported irregular cycles. After six months, a significant increase (p = 0.021) in patients with regular menstrual cycles was observed, with 19 reporting regular cycles, while only 3 continued to experience irregular cycles. Limitations, reasons for caution Several limitations of the study should be considered, including the small sample size and the relatively short six-month follow-up period. It would be valuable to compare the study participants with a control group of women who achieved weight loss through diet and exercise. Wider implications of the findings The convergence of BS and fertility is an area of significant interest and clinical impact. This study suggests that BS has no significant impact on AMH levels or ovarian reserve in short-term. However, extending the study’s follow-up period would provide valuable insights into the long-term effects on ovarian reserve. Trial registration number not applicable

The impact of ovarian endometrioma and endometriotic cystectomy on anti-Müllerian hormone, and antral follicle count: a contemporary critical appraisal of systematic reviews.

Currently, three crucial questions regarding the reliability of ovarian reserve measures in women with ovarian endometrioma during the reproductive age are being discussed. Firstly, the effects of endometriotic cystectomy on short and long-term ovarian reserve. Secondly, the accuracy of serum anti-Müllerian hormone (AMH) and antral follicle count (AFC) in estimating ovarian reserve in these cases. Thirdly, the impact of endometrioma itself on the ovarian reserve over time in such cases. The purpose of the present review is to critically assess available systematic reviews and meta-analyses that have explored these questions. Nine eligible reviews were found following a systematic search on PubMed.com and similarly assessed. These reviews varied considerably regarding the level of evidence, as per an identical comprehensive scoring system. Moderate to high-quality evidence demonstrates that endometriotic cystectomy, by the stripping technique, adversely affects ovarian reserve in the short and long term, up to 9-18 months post-surgery. Damage to ovarian reserve was considerable but more pronounced in bilateral cases than unilateral cases, equivalent to 39.5% and 57.0%, respectively. Repeat endometriotic cystectomy is detrimental to ovarian reserve. The impact of endometrioma diameter on ovarian reserve before or after surgery is still unclear. Moderate to high-quality evidence, relying on simultaneous assessment of both ovarian reserve measures, shows that AMH is sensitive while AFC is not in cases undergoing ovarian cystectomy. AMH should be the biomarker of choice for counseling and managing women with endometrioma in their reproductive age, especially before surgery. While there is some evidence to show that endometrioma per se may harm ovarian reserve, this evidence is not robust, and there is good-quality evidence to challenge this notion. It is necessary to conduct further targeted RCTs, systematic reviews, and meta-analyses based on solid methodological grounds to increase the level of evidence, refine quantitative estimates, investigate open questions, and decrease heterogeneity.

Urinary benzophenone-3 concentrations and ovarian reserve in a cohort of subfertile women

ObjectiveTo evaluate the association between urinary benzophenone-3 concentrations and measures of ovarian reserve (OR) among women in the Environment and Reproductive Health (EARTH) Study seeking fertility treatment at Massachusetts General Hospital in Boston, Massachusetts. DesignProspective cohort study. MethodsWomen from the EARTH cohort contributed spot urine samples before assessment of OR outcomes. Antral follicle count (AFC) and day-3 follicle stimulating hormone (FSH) levels were evaluated as part of standard infertility workups during unstimulated menstrual cycles. Quasi-Poisson and linear regression models were used to evaluate the association of specific gravity (SG)-adjusted urinary benzophenone-3 concentrations with AFC and FSH, respectively, with adjustment for age and physical activity. In secondary analyses, models were stratified by age. Sensitivity analyses assessed for confounding by season by restricting to women with exposure and outcome measured in the same season and stratifying by summer vs. non-summer months and for confounding by sunscreen use by restricting to women who filled out product questionnaires and adjusting for and stratifying by average sunscreen use score. ResultsThe study included 142 women (mean age ± SD, 36.1 ± 4.6; range, 22-45 years) enrolled between 2009 and 2017 with both urinary benzophenone-3 and AFC and 57 women with benzophenone-3 and FSH measurements. Most women were white (78%) and highly educated (49% with a graduate degree). Women contributed a mean of 2.7 urine samples (range, 1-10) with 37% contributing 2 or more samples. Benzophenone-3 was detected in 98% of samples. Geometric mean (GM) SG-corrected urinary benzophenone-3 concentration was 85.9 μ g/L (geometric standard deviation 6.2). There were no associations of benzophenone-3 with AFC and day-3 FSH in the full cohort. In stratified models, a 1-unit increase in log GM benzophenone-3 was associated with AFC 0.91 (95% CI, 0.86, 0.97) times lower among women ≤35 years old and was associated with FSH 0.73 (95% CI, 0.12, 1.34) IU/L higher among women >35 years old. Effect estimates from models stratified by season and sunscreen use were null. ConclusionIn main models, urinary benzophenone-3 was not associated with OR. However, younger may be vulnerable to potential effects of benzophenone-3 on AFC. Further research is warranted.

Laparoscopically confirmed endometriosis and anti-Müllerian hormone levels: Findings from the Nurses' Health Study II

ObjectiveAnti-Müllerian hormone is a reliable measure of ovarian reserve associated with menopause timing and fertility. Previous studies have observed that individuals with endometriosis have lower anti-Müllerian hormone levels than those without. However, sample sizes have been small and information is limited regarding the long-term influence of endometriosis on anti-Müllerian hormone levels among the general population, which may have important implications for menopause timing and chronic disease risk. MethodsAmong 1961 premenopausal women in the Nurses' Health Study II who provided a blood sample and had not been pregnant in the last 6 months, we used generalized linear models to determine the association between laparoscopically-confirmed endometriosis and log-transformed plasma anti-Müllerian hormone level, adjusted for age (continuous and squared) and other potential confounding variables. ResultsParticipants were on average 40 years old (interquartile range 37–42 years) at blood draw. Women with endometriosis diagnosed prior to blood draw (n = 119) had a lower mean anti-Müllerian hormone level (1.6 ng/mL [SD = 2.3]) than women without known endometriosis (n = 1842) (2.8 ng/mL [SD = 3.0]). In multivariable adjusted models, women with endometriosis had 29.6 % lower anti-Müllerian hormone levels (95 % CI: −45.4, −9.2 %) than women without. This association was greater among women with a body mass index of 25 kg/m2 or more (percent difference: −44.0 % (−63.7, −13.8)), compared to those with a body mass index of under 25 kg/m2 (percent difference: −19.8 % (−41.7, 10.4)), but did not vary by parity or infertility history. ConclusionsLower anti-Müllerian hormone levels in women with endometriosis may be one mechanism through which endometriosis influences risk of infertility, younger age at menopause, and cardiovascular disease.

SHORTER TELOMERE LENGTH IS ASSOCIATED WITH LOWER ANTRAL FOLLICLE COUNT AND POORER IN VITRO FERTILIZATION OUTCOMES IN WOMEN OF ADVANCED REPRODUCTIVE AGE

To determine if telomere length in peripheral blood mononuclear cells (PBMCs) is associated with ovarian reserve measures and in vitro fertilization (IVF) outcomes in women of advanced reproductive age.

A study to correlate serum anti mullerian hormone, basal follicle stimulating hormone and antral follicle count in primary infertility as a measure of ovarian reserve

A study to correlate serum anti mullerian hormone, basal follicle stimulating hormone and antral follicle count in primary infertility as a measure of ovarian reserve

Comparison of the Effect on the Ovarian Reserve of Modern Methods of Treatment of Endometrioid Cysts

ObjectiveTo compare the efficacy and safety of autologous platelet-rich plasma (PRP) therapy in laparoscopy and transvaginal sclerotherapy for the treatment of endometrioid cysts for maintaining ovarian reserve. MethodsThe study included 71 women under age 35 years with primary and secondary infertility. Twenty women underwent sclerotherapy of endometrioid cysts followed by autologous PRP injection into ovarian tissue, and 21 underwent laparoscopic cyst removal by stripping followed by autologous PRP injection. The control group consisted of 30 women who underwent laparoscopic cystectomy by stripping without autologous PRP injection. We assessed ovarian reserve for all patients before surgery as well 3 and 6 months after surgery by measuring serum anti-Müllerian hormone (AMH) levels and calculating antral follicle count using ultrasound. ResultsIn the control group, AMH levels had decreased significantly at 3 and 6 months post-surgery, whereas levels in laparoscopy and PRP group remained almost unchanged from initial levels. In the sclerotherapy group, we observed a tendency towards increased AMH levels, but it was not statistically significant when compared with initial results. Follicle count changes were similar to AMH patterns. ConclusionIn this study, sclerotherapy in combination with PRP therapy for ovarian endometriomas was associated with improved measures of ovarian reserve, and the combination of laparoscopic excision of the endometrioma with PRP therapy facilitated ovarian reserve preservation.

P–551 Blastocyst cohort size is not associated with embryo aneuploidy: comprehensive multi-centre data from current preimplantation genetic testing cycles

Abstract Study question Does blastocyst cohort size impact aneuploidy rates, evaluated by next generation sequencing (NGS)? Summary answer Embryo aneuploidy rates were independent of blastocyst cohort size across all patient ages. What is known already The effects of ovarian response on oocyte and embryo quality remain controversial. Several studies have proposed that a high response to ovarian stimulation may negatively impact oocyte competence. Alternatively, irrespective of maternal age, a poor ovarian response may potentially compromise embryo quality. Using blastocyst cohort size as an indirect measure of ovarian response, previous studies applying array comparative genomic hybridisation (aCGH) have demonstrated that the number of embryos available for biopsy does not impact embryo aneuploidy rates. Nevertheless, these findings remain to be confirmed in a comprehensive cohort, using current approaches for preimplantation genetic testing for aneuploidies (PGT-A). Study design, size, duration Retrospective, international, cohort study of 3998 patients from 16 clinics undergoing PGT-A from 2016–2020. We evaluated 11665 blastocysts, tested using trophectoderm (TE) biopsy and next generation sequencing (NGS). To eliminate bias of multiple treatments, we considered only the first PGT-A cycle for all patients. Both autologous and donation cycles were included in the analysis. Cycles were excluded if they utilised preimplantation genetic testing for monogenic disorders (PGT-M) or preimplantation genetic testing for structural rearrangements (PGT-SR). Participants/materials, setting, methods We evaluated aneuploidy and mosaicism rates, as well as the proportion of patients who had at least one euploid embryo suitable for transfer. Findings were stratified according to SART-defined maternal age groups, &amp;lt;35 (n = 698/2622 patients/blastocysts), 35–37 (n = 988/3141 patients/blastoycsts), 38–40 (n = 1447/3939 patients/blastocysts), 41–42 (653/1562 patients/blastocysts) and &amp;gt;42 (212/401 patients/blastocysts) and blastoycst cohort size (1–2, 3–5, 6–9 and 10 or more biopsied blastocysts). Main results and the role of chance The mean maternal age was 37.0±3.7. The overall embryo aneuploidy rate was 50.6% (5904/11665), while mosaicism was established in 4.0% (469/11665) of blastocysts. As expected, the proportion of aneuploid embryos increased steadily with advancing maternal age (31.8%, 41.5%, 58.4%, 71.2%, 87.8%; p &amp;lt; 0.0001), while mosaicism rates did not vary significantly (p = 0.2). Within each age group, we observed no association between the number of blastocysts biopsied and aneuploidy or mosaicism rates. However, as previously suggested, the chance of having at least one euploid embryo increased linearly with the number of embryos biopsied. We observed that young patients (&amp;lt;35) with 1–2 blastocysts had a 70.4% of having at least one embryo suitable for transfer, which increased to 96.4% and 99.2% with 3–5 and 6–9 blastocysts, respectively. Similar trends were observed in the 36–38 and 39–40 age groups. Patients in the 40–41 age group had a significantly lower chance of having a suitable embryo for transfer. Nevertheless, the chance increased from 27.2% with 1–2 embryos to 61.2% with 3–5 blastocysts. Patients with &amp;gt;10 embryos had at least one euploid embryo in 100% of cases, across all ages. Albeit, the numbers of patients within this category was low, and decreased significantly with advancing maternal age. Limitations, reasons for caution While blastocyst cohort size is considered to be an indirect measure of ovarian reserve, the number of oocytes retrieved was not evaluated. Our study only included the first PGT-A cycle for all patients. Subsequent, alterations in stimulation protocols may have resulted in an improved response in some patients. Wider implications of the findings: The comprehensive nature of the study, based on current PGT-A approaches and a large number of cycles across 16 centres increases clinical confidence in the notion that ovarian response is independent of embryo aneuploidy. Importantly, our findings may serve as a valuable clinical resource to guide patient counselling strategies. Trial registration number NA

Impact of ambient temperature on ovarian reserve

To examine the association between ambient temperature and antral follicle count (AFC), a standard measure of ovarian reserve. Prospective cohort study. Fertility center at an academic hospital in the northeastern United States. 631 women attending the Massachusetts General Hospital Fertility Center (2005-2015) who participated in the Environment and Reproductive Health Study. Daily temperature at the women's residential address was estimated for the 90 days before their antral follicle scan using a spatially refined gridded climate data set. We evaluated the associations between temperature and AFC using Poisson regression with robust standard errors, adjusting for relative humidity, fine particulate matter exposure, age, education, smoking status, year and month of AFC, and diagnosis of diminished ovarian reserve and ovulation disorders. Antral follicle count as measured with transvaginal ultrasonography. A 1°C increase in average maximum temperature during the 90 days before ovarian reserve testing was associated witha -1.6% (95% confidence interval [CI], -2.8, -0.4) lower AFC. Associations remained negative, but were attenuated, for average maximum temperature exposure in the 30 days (-0.9%, 95% CI, -1.8, 0.1) and 14 days (-0.8%, 95% CI, -1.6, 0.0) before AFC. The negative association between average maximum temperature and AFC was stronger in November through June than during the summer months, suggesting that timing of heat exposure and acclimatization to heat may be important factors to consider in future research. Exposure to higher temperatures was associated with lower ovarian reserve. These results raise concern that rising ambient temperatures worldwide may result in accelerated reproductive aging among women.

Anti- Müllarian hormone (AMH) as an indicator of ovarian reserve in acne patients treated with isotretinoin

Background: Isotretinoin suppresses sebum development by inducing sebocyte apoptosis, which is induced by the expression of tumour necrosis factor-related apoptosis-inducing ligand, insulin-like growth factor binding protein-3, and neutrophil gelatinase-associated lipocalin, which is induced by isotretinoin. While apoptosis could play a role in the drug's key mechanism of action, it may also be to blame for the majority of isotretinoin's side effects, including ovarian reserve impairment. The aim of this study was to see if AMH could be used as a measure of ovarian reserve in isotretinoin-treated acne patients. The participants in this study were 66 female patients in their reproductive years who had various degrees of acne. All of the patients were chosen from the Dermatology and Andrology Department of Benha University Hospitals' outpatient clinic. The research lasted anywhere from 6 to 12 months. The average age of the patients in this study was 25 years, with a standard deviation of 6 years. There was no substantial difference in AMH before and after Isotretinoin therapy. The percentage change in AMH after treatment had no important relationship with the patients' age, Isotretinoin dosage, or treatment period. Isotretinoin has a negative impact on the ovaries, according to the findings. More research is required to gain a better understanding of this subject and to see if the effects are permanent.

Factors affecting the accuracy and reliability of the measurement of anti-Müllerian hormone concentration in the clinic.

ObjectiveWe aimed to identify the factors that influence serum anti-Müllerian hormone (AMH) concentration measurements.MethodsWe collected serum samples between May and September 2018 and compared the effect on AMH concentration measured by ELISA of conditions including venepuncture, storage time, storage temperature, locations of the reaction microplate, and the use of the oral contraceptive pill and gonadotrophin-releasing hormone (GnRH).ResultsAMH concentration was not affected by food intake but was affected by haemolysis. It was also much higher in samples on the edge of the ELISA microtitre plate. AMH concentration increased after incubation at room temperature for 1 day, 4°C for 3 days, −20°C for 1 month and −40°C for 4 months, but no change occurred during storage at −80°C for 9 months. AMH concentration was high in patients following GnRH agonist treatment but was not affected by oral contraceptives.ConclusionsNo fasting is required prior to AMH measurement. Placement of serum samples on the edge of microtitre plates affects the results of the AMH ELISA. If serum samples cannot be assayed immediately, it is best to store them at −80°C. Basal AMH concentration cannot be used as a measure of ovarian reserve after GnRH agonist treatment.

Testing and interpreting measures of ovarian reserve: a committee opinion

Ovarian reserve is defined as the number of oocytes remaining in the ovary, or oocyte quantity (oocyte number). Markers of ovarian reserve include hormone levels and sonographically measured features of the ovaries. These markers can be useful as predictors of oocyte yield following controlled ovarian stimulation and oocyte retrieval. However, they are poor predictors of reproductive potential independently from age. This document replaces the document of the same name last published in 2012 (Fertil Steril 2012;98:1407-15).

Hydroxycarbamide exposure and ovarian reserve in women with sickle cell disease in the Multicenter Study of Hydroxycarbamide.

The application of modern ovarian reserve measures to women with sickle cell disease (SCD) may help answer longstanding questions about whether SCD or hydroxycarbamide (HC; also known as hydroxyurea) affect women's reproductive lifespan. Anti-Müllerian hormone (AMH), an established marker of ovarian reserve, is used to assess the ovarian follicle pool. We used a standard clinical assay to measure AMH in 285 banked samples from 93 female subjects with haemoglobin SS from the historic Multicenter Study of Hydroxyurea (MSH), which led to the United States Food and Drug Administration approval of HC for adults with SCD. No samples from the randomised portion of the MSH remain, so samples from the decade-long MSH follow-up studies were analysed. Most subjects were exposed to HC (86/93). The median AMH levels were lower in study subjects than in age- and sex-matched reference values. The median AMH levels consistent with diminished ovarian reserve, a risk factor for infertility, occurred in subjects starting at the age of 25-30years; in healthy women, this occurs after the age of 40years. In multivariate analysis, taking HC was independently associated with a low AMH (β = 0·001, 95% confidence interval -0·002 to 0·000; P=0·006). These results suggest that ovarian reserve is prematurely reduced in women with haemoglobin SS and raise the possibility that HC contributes to this finding.

Comparison between AMH level in Multipara and Nullipara in Women More than 40 Years Old

Decreased ovarian reserve is considered as one of the main causes of infertility. It is about the availability of preovulatory oocytes in the ovaries. With increase age, ovarian reserve decreases. Nowadays, “ovarian reserve” assessment became a strategy to assess female infertility.Objective: The current study aims to find the relationship between age and infertility type with measures of ovarian reserve (FSH, AMH and AFC) in infertile patients.Material and Method: The cross-sectional study design was used for this study and a survey was conducted among 100 infertile women.Result: Results revealed that Relationships between age and ovarian reserve indicators show a highly significant negative correlation with AFC (p= 0.001) and AMH (p= 0.007) level while positive correlation is found with FSH level (p= 0.001). The relation between age and FSH was moderate (rs=0.38, p&lt;0.0001) and revealed that AMH and AFC level decreases while FSH level increases with age.Conclusion Study of AMH level is the most reliable source to measure age-specific changes.

Anti-Mullerian Hormone, a Measure of Ovarian Reserve, Is Low in Female Subjects in the Multi-Center Study of Hydroxyurea

Introduction: Whether sickle cell disease (SCD) or its primary treatment, hydroxyurea (HU), limits reproductive potential in affected women is unknown. Females are born with a finite number of eggs. Anti-Mullerian Hormone (AMH), produced by immature ovarian follicles, is an established method to measure ovarian reserve. Two studies of AMH, one in adolescents with SCD and another in adult women with SCD exist, but neither normal AMH values nor the effect of HU on AMH are established in girls and women with SCD. The purpose of this study is to evaluate AMH levels in women who participated in the seminal study that led to FDA-approval for HU in adults with SCD, the Multi-Center Study of Hydroxyurea (MSH). Methods: The MSH was a randomized placebo-controlled trial (RCT) of HU. The RCT demonstrated HU's efficacy, so a 10-year MSH extension study was conducted to assess HU's potential for "mutagenesis, teratogenesis and oncogenesis". Although no samples from the RCT remain, serum samples (n=285) were available for many women in the follow-up study (n=93). We measured AMH in these samples using the CLIA-certified electrochemiluminescence assay in clinical use at our institution (Esoterix Labs, Calabasas Hills, CA). The assay's reference median AMH in women ages 26 - 30 years is 4.20 ng/mL, and in women 36 - 40 years is 1.69 ng/mL. The assay's lower limit of detection is 0.015ng/mL. Samples with AMH levels beneath the detection limit were run in duplicate when sufficient sample existed; this did not change any results. Here, we report AMH levels in female subjects (n=57) with a serum sample from the first annual follow-up visit (AV01). Descriptive statistics with median values reported for non-parametric variables (Mann Whitney U Test) were performed. AMH &amp;lt; 1 is associated with diminished ovarian reserve, a risk factor for shortened reproductive lifespan, infertility and poor outcomes with assisted reproductive technology. Therefore, we categorized AMH as normal (&amp;gt;/= 1 ng/ml) and low (&amp;lt;1 ng/ml). We initially evaluated factors associated with low AMH using the chi-squared and Mann Whitney U test for categorical and continuous variables, respectively. We then performed logistic regression analysis to evaluate the independent association of age, BMI, absolute neutrophil count (ANC), mean corpuscular volume (MCV) and months of HU exposure with AMH levels. Results: Samples from the first post-study visit were available for 57 women; the median time to first post-study visit was 31 months (IQR 6.5) after RCT closure. Median values for the cohort were: AMH, 0.306ng/ml (IQR 1.162), age, 32.50 years (IQR 11), MCV, 102.0 fl (IQR 15.8), and HU exposure, 23.92 months (IQR 30.72). Figure 1 shows AMH distribution in the cohort. AMH levels were low in 77% (44 of 57) of the cohort. Table 1 compares patient characteristics of subjects with low AMH (n=44) versus normal AMH (n=13). In univariate analysis, subjects with low AMH were older (34.5 vs 24.5, p&amp;lt;0.001) and had larger MCV (105.55 vs 95.80, p=0.002). Median HU exposure time did not reach significance between low and normal AMH groups (33 months vs 17 months, p=0.055). In a logistic regression model, age [OR 1.252, (95% CI 1.066, 1.014), p=0.006] and MCV [OR 1.139, (95% CI 1.014, 1.279), p=0.028] were associated with low AMH while duration of exposure to HU [OR 1.01 (95% CI 0.91, 1.09), p=0.364], body mass index [OR 1.07 (95% CI 0.91, 1.25), P=0.442] and ANC [OR 1.39 (95% CI 0.91, 2.13), p=0.127) were not associated with low AMH. Conclusions: Most women (77%) in this cohort had low AMH, associated with older age and higher MCV. This preliminary analysis raises concerns about diminished ovarian reserve in women with SCD. Although months of HU exposure was not associated with low AMH, HU exposure does not account for adherence, which is a major limitation in most sickle cell studies. MCV which increases with consistent HU use and is a biological proxy measure of the last 3-months of HU adherence, was associated with low AMH. Ovarian reserve was not a planned endpoint in the MSH. A prospective study of ovarian reserve in women with SCD is needed to understand how the physiology of SCD itself or exposure to HU may influence multiple fertility endpoints. Disclosures Chaturvedi: Shire/Takeda: Research Funding; Sanofi: Consultancy; Alexion: Consultancy. Lanzkron:PCORI: Research Funding; NIH: Research Funding; Pfizer: Research Funding; Global Blood Therapeutics: Research Funding; Ironwood: Research Funding; HRSA: Research Funding.

Reproductive Outcomes Following Uterine Artery Occlusion at the Time of Myomectomy: Systematic Review and Meta-analysis.

This investigation sought systematically to review and meta-analyze evidence on reproductive outcomes following uterine artery occlusion (UAO) at myomectomy. Databases searched included PubMed, EMBASE, Ovid MEDLINE, Web of Science, and ClinicalTrials.gov. Eligible studies included observational and randomized controlled trials in which patients underwent abdominal, laparoscopic, or robotic myomectomy and in which at least one measure of clinical pregnancy rate, live birth rate, or ovarian reserve was reported. The primary outcome was live birth rate. Secondary outcomes included clinical pregnancy rate, miscarriage rate, adverse pregnancy outcomes, and measures of ovarian reserve. Twelve articles involving 689 women were included in the systematic review. The intervention group underwent UAO at laparoscopic or abdominal myomectomy (UAO+M) (n = 470). The control group underwent myomectomy alone (n = 219). Seven articles involving 420 women were included in the meta-analysis (201 underwent UAO+M; 219 underwent myomectomy alone). Live births occurred in 54 of 201 (27%) women in the UAO+M group and in 74 of 219 (34%) women in the control group. Clinical pregnancies occurred in 73 of 201 (36%) women in the UAO+M group and in 102 of 219 (47%) control subjects. There was no difference in live birth rates (odds ratio 0.89; 95% CI 0.56-1.43; P = 0.51; 7 studies, 420 patients) or clinical pregnancy rates (odds ratio 0.81; 95% confidence interval 0.53-1.24; P = 0.33; 7 studies, 420 patients) between the UAO+M and control groups. Data on miscarriage rates, adverse pregnancy outcomes, and measures of ovarian reserve precluded meta-analysis. In conclusion, UAO at myomectomy is not associated with reductions in live birth or clinical pregnancy rates. Before routine use can be recommended in women desiring future fertility, more research is required on reproductive outcomes and effects on ovarian reserve.

Predicting the chances of having a baby with or without treatment at different time points in couples with unexplained subfertility.

Can we develop a prediction model that can estimate the chances of conception leading to live birth with and without treatment at different points in time in couples with unexplained subfertility? Yes, a dynamic model was developed that predicted the probability of conceiving under expectant management and following active treatments (in vitro fertilisation (IVF), intrauterine insemination with ovarian stimulation (IUI + SO), clomiphene) at different points in time since diagnosis. Couples with no identified cause for their subfertility continue to have a realistic chance of conceiving naturally, which makes it difficult for clinicians to decide when to intervene. Previous fertility prediction models have attempted to address this by separately estimating either the chances of natural conception or the chances of conception following certain treatments. These models only make predictions at a single point in time and are therefore inadequate for informing continued decision-making at subsequent consultations. A population-based study of 1316 couples with unexplained subfertility attending a regional clinic between 1998 and 2011. A dynamic prediction model was developed that estimates the chances of conception within 6months from the point when a diagnosis of unexplained subfertility was made. These predictions were recomputed each month to provide a dynamic assessment of the individualised chances of conception while taking account of treatment status in each month. Conception must have led to live birth and treatments included clomiphene, IUI + SO, and IVF. Predictions for natural conception were externally validated using a prospective cohort from The Netherlands. A total of 554 (42%) couples started fertility treatment within 2years of their first fertility consultation. The natural conception leading to live birth rate was 0.24 natural conceptions per couple per year. Active treatment had a higher chance of conception compared to those who remained under expectant management. This association ranged from weak with clomiphene to strong with IVF [clomiphene, hazard ratio (HR) = 1.42 (95% confidence interval, 1.05 to 1.91); IUI + SO, HR = 2.90 (2.06 to 4.08); IVF, HR = 5.09 (4.04 to 6.40)]. Female age and duration of subfertility were significant predictors, without clear interaction with the relative effect of treatment. We were unable to adjust for other potentially important predictors, e.g. measures of ovarian reserve, which were not available in the linked Grampian dataset that may have made predictions more specific. This study was conducted using single centre data meaning that it may not be generalizable to other centres. However, the model performed as well as previous models in reproductive medicine when externally validated using the Dutch cohort. For the first time, it is possible to estimate the chances of conception following expectant management and different fertility treatments over time in couples with unexplained subfertility. This information will help inform couples and their clinicians of their likely chances of success, which may help manage expectations, not only at diagnostic workup completion but also throughout their fertility journey. This work was supported by a Chief Scientist Office postdoctoral training fellowship in health services research and health of the public research (ref PDF/12/06). B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck, and Guerbet. None of the other authors declare any conflicts of interest.

Differential Rates of Change in Measures of Ovarian Reserve in Young Cancer Survivors Across the Reproductive Lifespan.

Recent studies have examined level and rate of change of anti-Müllerian hormone (AMH) for predicting time to menopause. Limited prospective, longitudinal data exists evaluating measures of ovarian reserve (MOR) in cancer survivors. Determine the rate of change of MOR in survivors (15 to 39 years) compared with similar-aged controls and compared with late reproductive-aged controls (40 to 50 years). Prospective cohort. Quaternary university hospital. Survivors at least 1 year from therapy completion, similar-aged controls, and late reproductive-aged controls. Annual visits with early follicular-phase hormone analysis and ultrasound. Changes in AMH and antral follicle count (AFC) were modeled using random effects linear regression. Cancer survivors (170) and 135 similar-aged controls had annual visits for an average of 38 months; 71 late reproductive-aged controls were followed for an average of 24 months. In models adjusted for body mass index, time since cancer therapy (for survivors), and exogenous hormone use, the geometric mean AMH and AFC levels were lower in the survivors than similar-aged controls at all ages. After age 24.5 AMH and AFC declined in both groups at rates that were similar (P = 0.78 for AMH, P = 0.37 for AFC). Late reproductive-aged controls declined at a much more precipitous rate of 30% per year for AMH and 16% per year for AFC (P < 0.01 compared with survivors). Although survivors had lower levels of AMH and AFC at the time of enrollment, the rate of change of AMH and AFC is not significantly different than similar-aged controls.

Assessment of ovarian reserve after cystectomy versus 'one-step' laser vaporization in the treatment of ovarian endometrioma: a small randomized clinical trial.

STUDY QUESTIONDoes CO2 laser vaporization offer better results in treating endometrioma in terms of ovarian reserve preservation compared to traditional cystectomy?SUMMARY ANSWERAssessing both antral follicle count (AFC) and serum anti-Müllerian hormone (AMH) levels as measures of ovarian reserve, the results suggest that CO2 technology may be an alternative treatment for endometrioma, causing minimal damage to adjacent healthy ovarian tissue.WHAT IS KNOWN ALREADYExcisional surgery has been questioned as an ideal surgical approach for endometriomas because it is associated with potential reduction of ovarian reserve. Recently, vaporization with CO2 laser in-line-of-sight, according to the ‘three-step procedure’, has been proposed as the best method to preserve ovarian function. However, no randomized controlled trials have been conducted to compare cystectomy and ‘one-step’ CO2 fiber laser vaporization (without GnRH agonist therapy) with respect to the ovarian reserve.STUDY DESIGN, SIZE, DURATIONA multicentre randomized clinical trial including 60 patients was performed between July 2017 and February 2018. Computerized randomization was conducted to allocate them in a proportion of 1:1 either to Group 1 (laparoscopic stripping: cystectomy) or Group 2 (CO2 laser vaporization). Patients in Group 1 underwent a standardized laparoscopic stripping technique; patients in Group 2 underwent drainage of the cyst content, biopsy and vaporization of the internal wall with a CO2 fiber laser. Patients underwent pelvic ultrasound examination to determine the AFC and blood sampling to determine AMH levels before surgery and at 1- and 3-month follow-up.PARTICIPANTS/MATERIALS, SETTING, METHODSPatients undergoing surgery for symptomatic endometriomas (infertility and/or pelvic pain) larger than 3 cm were randomized in two groups according to the surgical technique. Patients aged ≥40 years, or with deep infiltrating endometriosis/adenomyosis, or previously submitted to surgical procedures on the ovaries or to hysterectomy were excluded from the study. The primary endpoint was the comparison of intra-group AFC changes before and after surgery (ΔAFC) between the two groups (ΔAFC Group 1 versus ΔAFC Group 2). The secondary endpoint was the modification of serum AMH before and after surgery (ΔAMH) between the two groups (ΔAMH Group 1 versus ΔAMH Group 2).MAIN RESULTS AND THE ROLE OF CHANCEThe AFC of the operated ovary was significantly increased in Group 2 (laser vaporization) compared with Group 1 (cystectomy) after surgery (Group 1: from 4.1 ± 2.2 [mean ± SD] at baseline to 6.3 ± 3.5 at 3-month follow-up; 95% CI: 0.9–4; Group 2: from 3.6 ± 1.9 at baseline to 8.6 ± 4.2 at 3-month follow-up; 95% CI: 2.8–7.1; P = 0.016); serum AMH levels were significantly reduced at 3 months in Group 1 (from 2.6 ± 1.4 ng/mL at baseline to 1.8 ± 0.8 ng/mL at 3-month follow-up; 95% CI: −1.3 to −0.2; P = 0.012) compared with no reduction in Group 2 (from 2.3 ± 1.1 ng/mL at baseline to 1.9 ± 0.9 ng/mL at 3-month follow-up; 95% CI: −1 to −0.2; P = 0.09).LIMITATIONS, REASON FOR CAUTIONThe key limitations of the trial were the low accuracy of AFC in estimating the ovarian reserve in ovaries with endometriomas, the limited study size and the relatively short follow-up, which do not allow us to draw definitive conclusions.WIDER IMPLICATIONS OF THE FINDINGSThe present study suggests that CO2 technology may treat endometrioma with minimal damage to the adjacent healthy ovarian tissue; however, this study should be considered as a preliminary clinical trial, intended to stimulate future larger trials to address this clinically relevant issue.STUDY FUNDING/COMPETING INTEREST(S)None.TRIAL REGISTRATION NUMBERClinicalTrials.gov NCT03227640.TRIAL REGISTRATION DATE9 July 2017.DATE OF FIRST PATIENT’S ENROLLMENT24 July 2017.