Fast and furious: pregnancy outcome with one-step rehydration in the warming protocol for human blastocysts.

RESEARCH QUESTION: Do embryos warmed using a one-step rehydration protocol with a more efficient workflow result in comparable pregnancy rates to the standard multi-step rehydration protocol? DESIGN: A retrospective cohort study of 3439 frozen embryo transfers (FET). Clinical outcomes of 833 FETs using a one-step rehydration protocol were reviewed and compared with results from the control group (2606 FETs using standard multi-step rehydration protocol). Primary outcome was ongoing pregnancy rate. Secondary outcomes were survival, positive pregnancy, clinical pregnancy, implantation and miscarriage rates. RESULTS: Survival rates were identical between the two groups (99.5%). Clinical pregnancy rate was 63.0% in the one-step warming protocol, comparable to 59.9% in the multi-step rehydration protocol. A significant increase was observed in the ongoing pregnancy rate with 60.4% in the one-step rehydration versus 55.4% in the multi-step rehydration group (P = 0.011); implantation rate was 63.6% versus 57.0% (P = 0.0005). The miscarriage rate of 4.0% in the one-step rehydration protocol was significantly lower compared with 7.6% in the multi-step rehydration protocol (P = 0.0001). Comparable outcomes persisted even when the analysis was extended to embryos that had and had not undergone preimplantation genetic testing (PGT), as well as day of development of the blastocysts. When controlling for variables of age, PGT, blastocyst development day and embryo expansion, rapid warming significantly increased chances of an ongoing pregnancy (adjusted OR 1.264, 95% CI 1.076 to 1.484). CONCLUSION: A one-step rehydration protocol resulted in identical survival rates and improved ongoing pregnancy rates compared with the multi-step rehydration technique.

Validation of prognosis-based in vitro fertilization grant selection criteria.

Objective: To validate a prognosis-based scoring system for in vitro fertilization (IVF) grant allocation. Design: Retrospective cohort study. Setting: A 501(c)(3) nonprofit foundation that awards donated IVF cycles and grants to those with demonstrated financial need. In contrast to lottery-based or subjective allocation systems, applications are scored according to medical prognostic criteria in addition to personal characteristics. Patients: Grant recipients from 2015 to 2019. Interventions: None. Main outcome measures: Live birth rate (LBR) and cumulative LBR (CLBR) among grant recipients were compared with 2019 Society for Assisted Reproductive Technology (SART) national averages. Results: A total of 435 applications were reviewed, with 59 grants awarded for 51 autologous IVF cycles, 6 donor oocyte cycles, and 2 gestational carrier cycles, resulting in 39 live births after initial embryo transfer (LBR 61.9%) and 43 CLBRs (CLBR 72.9%). Among autologous cycles, the mean (±SD=3.9 years) age was 31.8 years, and LBR and CLBR were 62.8% and 68.6% vs. 28.2% and 37.1% among all autologous SART cycles, respectively. A subanalysis of grant recipients aged <35 years (n=39) revealed LBR and CLBR of 66.7% and 74.4% vs. 40.7% and 47.8% among autologous SART cycles aged <35 years, respectively. Conclusions: A scoring system incorporating medical criteria identified IVF grant applicants with a high likelihood of achieving a LB. Although most IVF grant programs select recipients through a lottery or personal characteristics, a prognosis-based scoring system should be considered to maximize LBR in a limited resource setting.

Parent Perspective on Childhood Development after Assisted Reproductive Technology: A National Survey.

CONTEXT: There is limited understanding about parent perspectives of newborn development after assisted reproductive technology (ART). The use of ART is known to increase the risk of premature delivery and low birth weight. Both of these factors are associated with developmental delay. To our knowledge, no study has investigated how parents perceive their child's development after use of ART. AIMS: To investigate how the parent perspective of childhood development after ART use compares to the parent perspective of spontaneously conceived children. SETTINGS AND DESIGN: This is a digital survey collecting data on parent perspective of newborn development after ART and spontaneous conception. SUBJECTS AND METHODS: Invitation to participate was sent via E-mail to users of a (Ovia Health's) mobile parenting application (Ovia Parenting). Surveys were collected from August 30, 2018, to September 12, 2018, and a total of 1881 surveys were collected. STATISTICAL ANALYSIS USED: Analysis was performed with Chi-square cross-tabulations and ANOVA. RESULTS: Overall, 13,600 (12%) of users who were delivered the E-mail engaged with the content. Of those users, 2739 (20%) initiated the survey and 1881 (69%) completed the survey and were included in the analyses. When comparing spontaneous conception to ART, parents reported similar developmental milestones at most ages. A significant difference existed at 12 months where those who had used ART were more likely to report their child met all milestones. This difference did not persist for subsequent ages. CONCLUSIONS: From the parent perspective, children conceived using ART methods should be expected to meet the same age-based developmental milestones as their spontaneously conceived peers.

Salt-inducible Kinases Are Critical Determinants of Female Fertility.

Follicle development is the most crucial step toward female fertility and is controlled mainly by follicle-stimulating hormone (FSH). In ovarian granulosa cells (GCs), FSH activates protein kinase A by increasing 3',5'-cyclic adenosine 5'-monophosphate (cAMP). Since cAMP signaling is impinged in part by salt-inducible kinases (SIKs), we examined the role of SIKs on the regulation of FSH actions. Here, we report that SIKs are essential for normal ovarian function and female fertility. All SIK isoforms are expressed in human and rodent GCs at different levels (SIK3>SIK2>SIK1). Pharmacological inhibition of SIK activity potentiated the stimulatory effect of FSH on markers of GC differentiation in mouse, rat, and human GCs and estradiol production in rat GCs. In humans, SIK inhibition strongly enhanced FSH actions in GCs of patients with normal or abnormal ovarian function. The knockdown of SIK2, but not SIK1 or SIK3, synergized with FSH on the induction of markers of GC differentiation. SIK inhibition boosted gonadotropin-induced GC differentiation in vivo, while the genomic knockout of SIK2 led to a significant increase in the number of ovulated oocytes. Conversely, SIK3 knockout females were infertile, FSH insensitive, and had abnormal folliculogenesis. These findings reveal novel roles for SIKs in the regulation of GC differentiation and female fertility, and contribute to our understanding of the mechanisms regulated by FSH. Furthermore, these data suggest that specific pharmacological modulation of SIK2 activity could be of benefit to treat ovulatory defects in humans and to increase the propagation of endangered species and farm mammals.

Evaluating the Utility of Intralipid Infusion to Improve Live Birth Rates in Patients with Recurrent Pregnancy Loss or Recurrent Implantation Failure.

CONTEXT: Intralipid is used to improve clinical outcomes in patients with recurrent pregnancy loss (RPL) or recurrent implantation failure (RIF) with elevated natural killer (NK) cells. Data supporting this practice is conflicting but suggestive of minimal benefit. AIMS: The aims of this study are to determine if intralipid infusion improves live birth rates and if is a cost-effective therapy in the RPL/RIF population. SETTINGS AND DESIGN: This was a large REI private practice, retrospective cohort study. SUBJECTS AND METHODS: Charts of 127 patients who received intralipid from 2012 to 2015 were reviewed and compared to historical control data. T-tests and Chi-square analyses evaluated demographics and cycle statistics. Chi-square analyses assessed impact on clinical pregnancy and live birth rates. Cost analysis was performed from societal perspective with a one-way sensitivity analysis. RESULTS: Patients with live births were noted to have a higher average number of previous live births and were more likely to have had a frozen embryo transfer in the intralipid cycle in comparison to those with unsuccessful pregnancy outcomes. Neither clinical pregnancy nor live birth rates were significantly improved from baseline rates quoted in the literature (P = 0.12 and 0.80, respectively). Intralipid increased costs by $681 per live birth. If live birth rates were >40% using intralipid and <51% without intervention, neither strategy was favored. CONCLUSIONS: Intralipid does not improve live birth rates and is not cost-effective for patients with RIF or RPL and elevated NK cells. This study supports the growing literature demonstrating the minimal benefit of screening for and treating elevated peripheral NK cells.

The National Physicians Cooperative: transforming fertility management in the cancer setting and beyond.

Once unimaginable, fertility management is now a nationally established part of cancer care in institutions, from academic centers to community hospitals to private practices. Over the last two decades, advances in medicine and reproductive science have made it possible for men, women and children to be connected with an oncofertility specialist or offered fertility preservation soon after a cancer diagnosis. The Oncofertility Consortium's National Physicians Cooperative is a large-scale effort to engage physicians across disciplines - oncology, urology, obstetrics and gynecology, reproductive endocrinology, and behavioral health - in clinical and research activities to enable significant progress in providing fertility preservation options to children and adults. Here, we review the structure and function of the National Physicians Cooperative and identify next steps.

Knowledge about Age-Related Decline in Fertility and Oocyte Cryopreservation: A National Survey.

CONTEXT: Women worldwide are delaying childbearing, but are they aware of the age-related decline in fertility? AIMS: The aim of this study is to investigate awareness of age-related decline in fertility and oocyte cryopreservation. SETTINGS AND DESIGN: A primary analysis of a cross-sectional electronic survey with a nationally representative sample of nulliparous women aged 25-45 years. SUBJECTS AND METHODS: A national online survey performed March 4-March 9, 2016. STATISTICAL ANALYSIS USED: A linear regression model and ANOVA tests were performed. RESULTS: A total of 1213 women completed the survey. A significant difference was discovered in fecundity knowledge between women who identified as in a partnership compared to those who did not. Partnered women were more likely to respond "know a lot" about the age-related decline in fertility, whereas unpartnered women were more likely to respond "never heard of it" (P < 0.01). Partnered women are also more likely to respond that they would have made different life choices had they been more knowledgeable about fertility at a younger age (P = 0.01). The majority of the survey population had heard of oocyte cryopreservation but did not know much about it. CONCLUSIONS: Slightly over half of participants had an understanding of the natural age-related decline in fertility. Having a partner significantly increased the likelihood that a woman reported more knowledge about fertility. More effort is necessary to educate all women on assisted reproductive technologies and the natural age-related decline in fertility, specifically single women of childbearing age.

Reasons Why Young Women Accept or Decline Fertility Preservation After Cancer Diagnosis.

OBJECTIVE: To understand young women's reasons for accepting or declining fertility preservation after cancer diagnosis to aid in the development of theory regarding decision making in this context. DESIGN: Qualitative descriptive. SETTING: Participants' homes or other private location. PARTICIPANTS: Twenty-seven young women (mean age, 29 years) diagnosed with cancer and eligible for fertility preservation. METHODS: Recruitment was conducted via the Internet and in fertility centers. Participants completed demographic questionnaires and in-depth semi-structured interviews. Tenets of grounded theory guided an inductive and deductive analysis. RESULTS: Young women's reasons for deciding whether to undergo fertility preservation were linked to four theoretical dimensions: Cognitive Appraisals, Emotional Responses, Moral Judgments, and Decision Partners. Women who declined fertility preservation described more reasons in the Cognitive Appraisals dimension, including financial cost and human risks, than women who accepted. In the Emotional Responses dimension, most women who accepted fertility preservation reported a strong desire for biological motherhood, whereas women who declined tended to report a strong desire for surviving cancer. Three participants who declined reported reasons linked to the Moral Judgments dimension, and most participants were influenced by Decision Partners, including husbands, boyfriends, parents, and clinicians. CONCLUSION: The primary reason on which many but not all participants based decisions related to fertility preservation was whether the immediate emphasis of care should be placed on surviving cancer or securing options for future biological motherhood. Nurses and other clinicians should base education and counseling on the four theoretical dimensions to effectively support young women with cancer.

Psychological Counseling of Female Fertility Preservation Patients.

Young cancer patients are increasingly interested in preserving their fertility prior to undergoing gonadotoxic therapies. Although the medical safety and treatment protocols for fertility preservation have been well documented, limited research has addressed the emotional issues that arise in fertility preservation patients. We briefly review the literature on the psychosocial issues in adult female fertility preservation treatment and describe our experiences within this patient population. Our findings suggest that several important issues to be addressed during the psychological counseling of adult female fertility preservation patients include: (1) preexisting psychological distress in patients undergoing treatment, (2) choice of fertility preservation strategy in the face of an uncertain relationship future, (3) decision making regarding use of third-party reproduction (e.g., sperm/egg donation, gestational surrogacy), (4) treatment expectations regarding pregnancy and miscarriage, (5) ethical issues related to treatment including the creation, cryopreservation, and disposition of embryos/oocytes, and (6) decision regret from patients who declined fertility preservation.

Fertility preservation outcomes may differ by cancer diagnosis.

CONTEXT: Cancer survival has improved significantly and maintaining fertility is both a major concern and an important factor for the quality of life in cancer patients. AIMS: To explore differences in oocyte stimulation for fertility preservation (FP) patients based on cancer diagnosis. SETTINGS AND DEIGN: Between 2005 and 2011, 109 patients elected to pursue FP at a single institution. MATERIALS AND METHOD: In vitro fertilization (IVF) outcome variables between four cancer diagnostic groups (breast, gynecologic, lymphoma/leukemia and other) and age-matched male factor or tubal factor infertility IVF control group were compared. STATISTICAL ANALYSIS: ANOVA and Chi-square analyses were employed to compare variables between the groups that were normally distributed. Kruskal-Wallis with subsequent Mann-Whitney U-test were used for data that were not normally distributed. RESULTS: Women with gynecologic malignancies were significantly older than the women in the other three groups, but tended to have a better ovarian response. Women with hematologic malignancies were most likely to have been exposed to chemotherapy and had the longest stimulations with a similar number of oocytes retrieved. The age-matched IVF controls had higher peak estradiol levels, number of oocytes obtained, and fertilization rates when compared to cancer patients with or without a history of prior chemotherapy. CONCLUSIONS: Factors including age, type of cancer and chemotherapy exposure, can influence response to ovarian stimulation. Discussing these findings with patients presenting for FP may aid in setting realistic treatment expectations.

Prospective study of depression and anxiety in female fertility preservation and infertility patients.

OBJECTIVE: To prospectively assess anxiety, depression, coping, and appraisal in female fertility preservation (FP) patients compared with infertile patients. DESIGN: Prospective pre- and post-treatment survey. SETTING: Academic medical center. PATIENT(S): Forty-seven women with cancer (FP patients) and 91 age-matched infertile patients. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Depression, anxiety, coping, infertility-related stress, appraisal of treatment, and medical outcomes. RESULT(S): FP patients reported more symptoms of anxiety and depression than infertile patients, but infertile patients' symptoms worsened over time; 44% of FP and 14% of infertile patients' scores exceeded the clinical cutoff for depression before treatment. The interval between surveys and medical treatment data did not predict changes in mood symptoms. Coping strategies and infertility-related stress did not differ between groups, and avoidant coping predicted higher depression and anxiety scores. CONCLUSION(S): FP patients reported more anxiety and depression than infertile patients at enrollment in treatment, with more than one-third of FP patients reporting clinically significant depressive symptoms. However, infertile patients' anxiety and depressive symptoms increased across treatment. This increase was not related to time between registration for IVF and oocyte retrieval or the medical aspects of treatment. FP and infertile patients should be provided psychologic consultation before treatment to identify mood and anxiety symptoms and to refer patients for counseling as needed to prevent worsening of symptoms.

Human ovarian tissue cortex surrounding benign and malignant lesions.

OBJECTIVE: To quantify the number of follicles in patients with ovarian pathologies, benign and malignant, in pregnant and nonpregnant states and to determine how the presence of ovarian masses and BRCA status affects follicular counts. MATERIALS AND METHODS: Slides from 134 reproductive-aged women undergoing oophorectomy were examined using light microscopy by 3 independent counters blinded to the diagnosis. In all, 20 patients had cancer, 69 had benign conditions, and 35 patients were BRCA+ or had a strong family history of breast and/or ovarian cancer. In all, 10 women were either pregnant or immediately postpartum. RESULTS: Patients undergoing risk-reducing surgery had significantly decreased follicle count compared to physiologic control. Patients with cancer had significantly decreased counts compared to all other groups. There were no differences within the benign cohort. CONCLUSIONS: When compared to benign masses, the cortex surrounding an ovarian malignancy has decreased follicle density. The stretch impact may minimize any impact on total follicle numbers. Furthermore, there may be a proliferation of ovarian stroma, with the same number of follicles spread over a larger surface area. This information is important when counseling women with ovarian masses regarding the use of ovarian tissue cryopreservation.

Role of complementary and alternative medicine to achieve fertility in uninsured patients.

UNLABELLED: Among those facing infertility in the United States, underinsured and uninsured women are at the greatest disadvantage. Women who receive medical care under Medicaid are rarely covered for infertility testing; only 4 states will cover infertility treatment as an element of family planning and preconception care. Studies exploring the use of complementary and alternative medicine (CAM) in infertility patients have focused on patients who have insurance. We conducted a review of the literature via MEDLINE. Articles were limited to English-language, human studies published between 1990 and 2011. Significant disparities exist in access to infertility treatment based on race and ethnicity, household income, and level of education, even in states with mandated insurance coverage. Given the steep costs of assisted reproductive technologies, many infertility patients augment traditional medical treatment with CAM. Acupuncture and herbal supplements are the most studied therapies. Although dietary supplementsmay enhance fertility, the use of othermore expensive forms of CAM such as acupuncture has had mixed results. Complementary and alternative medicine may be a viable option for infertility care for uninsured patients who cannot otherwise afford treatment. TARGET AUDIENCE: Obstetricians and gynecologists, family physicians LEARNING OBJECTIVES: After completing this CME activity, physicians should be better able to analyze the effects that health care disparities have on fertility treatments for uninsured and underinsured women and evaluate the literature to determine which complementary and alternative treatments for infertility can improve fertility.

Laparoscopic tubal reanastomosis versus in vitro fertilization: cost-based decision analysis.

OBJECTIVE: Regret after tubal ligation continues to be a problem. After tubal ligation, couples have the option of tubal surgery or in vitro fertilization (IVF). STUDY DESIGN: Using decision analysis techniques, we compared cost-effectiveness of tubal reanastomosis by tubal type vs tubal surgery or in vitro fertilization (IVF) for 3 separate age groups of women: <35 years of age, 35 to 40 years of age and >40 years of age. Tubal techniques was divided into type A, those with more favorable prognosis because of the likelihood of having a more significant length tube at time of reanastomosis and type B, those with a worse prognosis of success. We incorporated delivery costs to address the impact of high order multiples in IVF. Data were extracted by studies available in the literature. All costs were adjusted to 2012 US dollars. One-way and 2-way sensitivity analyses were performed. RESULTS: The laparoscopic reanastomosis of type A dominated the other groups, because it was more effective and less costly then type B and IVF. However, when women were >40 years old with a history of type B, IVF was favored when its costs were at the lower limit. CONCLUSION: The most cost-effective choice for a woman desiring pregnancy after tubal ligation is laparoscopic reanastomosis after a prior clip or ring tubal ligation for women ≤40 years old. It is also the most cost-effective for the oldest cohort, assuming IVF costs are greater than $4500.

IGF-I signaling is essential for FSH stimulation of AKT and steroidogenic genes in granulosa cells.

FSH and IGF-I synergistically stimulate gonadal steroid production; conversely, silencing the FSH or the IGF-I genes leads to infertility and hypogonadism. To determine the molecular link between these hormones, we examined the signaling cross talk downstream of their receptors. In human and rodent granulosa cells (GCs), IGF-I potentiated the stimulatory effects of FSH and cAMP on the expression of steroidogenic genes. In contrast, inhibition of IGF-I receptor (IGF-IR) activity or expression using pharmacological, genetic, or biochemical approaches prevented the FSH- and cAMP-induced expression of steroidogenic genes and estradiol production. In vivo experiments demonstrated that IGF-IR inactivation reduces the stimulation of steroidogenic genes and follicle growth by gonadotropins. FSH or IGF-I alone stimulated protein kinase B (PKB), which is also known as AKT and in combination synergistically increased AKT phosphorylation. Remarkably, blocking IGF-IR expression or activity decreased AKT basal activity and abolished AKT activation by FSH. In GCs lacking IGF-IR activity, FSH stimulation of Cyp19 expression was rescued by overexpression of constitutively active AKT. Our findings demonstrate, for the first time, that in human, mouse, and rat GCs, the well-known stimulatory effect of FSH on Cyp19 and AKT depends on IGF-I and on the expression and activation of the IGF-IR.

Toward theoretical understanding of the fertility preservation decision-making process: examining information processing among young women with cancer.

BACKGROUND: Young women with cancer now face the complex decision about whether to undergo fertility preservation. Yet little is known about how these women process information involved in making this decision. OBJECTIVE: The purpose of this article is to expand theoretical understanding of the decision-making process by examining aspects of information processing among young women diagnosed with cancer. METHODS: Using a grounded theory approach, 27 women with cancer participated in individual, semistructured interviews. Data were coded and analyzed using constant-comparison techniques that were guided by 5 dimensions within the Contemplate phase of the decision-making process framework. RESULTS: In the first dimension, young women acquired information primarily from clinicians and Internet sources. Experiential information, often obtained from peers, occurred in the second dimension. Preferences and values were constructed in the third dimension as women acquired factual, moral, and ethical information. Women desired tailored, personalized information that was specific to their situation in the fourth dimension; however, women struggled with communicating these needs to clinicians. In the fifth dimension, women offered detailed descriptions of clinician behaviors that enhance or impede decisional debriefing. CONCLUSION: Better understanding of theoretical underpinnings surrounding women's information processes can facilitate decision support and improve clinical care.