Providers' perspectives on the reproductive decision-making of BRCA-positive women.

BACKGROUND: Reproductive decision-making is difficult for BRCA-positive women. Our objective was to assess the complexities of decision-making and identify decisional supports for patients and providers when discussing reproductive options prior to risk-reducing salpingo-oophorectomy (RRSO). METHODS: This study was of qualitive design, using data collection via semi-structured interviews conducted from November 2018 to October 2020. Individuals were included if they were identified to provide care to BRCA-positive women. In total, 19 providers were approached and 15 consented to participate. Providers were recruited from three clinics in Toronto, Ontario located at academic centers: [1] A familial ovarian cancer clinic, [2] A familial breast cancer clinic and [3] A fertility clinic, all of which treat carriers of the BRCA1/BRCA2 genetic mutation. The interview guide was developed according to the Ottawa Decision Support Framework and included questions regarding reproductive options available to patients, factors that impact the decision-making process and the role of decisional support. Interviews were transcribed and transcripts were analyzed thematically using NVIVO 12. RESULTS: Providers identified three major decisions that reproductive-aged women face when a BRCA mutation is discovered: [1] "Do I want children?"; [2] "Do I want to take the chance of passing on this the mutation?"; and [3] "Do I want to carry a child?" Inherent decision challenges that are faced by both providers and patients included difficult decision type, competing options, scientifically uncertain outcomes, and challenging decision timing. Modifiable decisional needs included: inadequate knowledge, unrealistic expectations, unclear values and inadequate support or resources. Identified clinical gaps included counselling time constraints, lack of reliable sources of background information for patients or providers and need for time-sensitive, geographically accessible, and centralized care. CONCLUSION: Our study identified a need for a patient information resource that can be immediately provided to patients who carry a BRCA genetic mutation. Other suggestions for clinical practice include more time during consultation appointments, adequate follow-up, value-centric counseling, access to psychosocial support, and a specialized decisional coach.

Ovarian function after chemotherapy in young breast cancer survivors.

BACKGROUND: As cure rates for breast cancer improve, there is increasing evidence that late effects of treatment-and impaired fertility in particular-are emerging as important concerns among young breast cancer survivors. Older reports have evaluated the occurrence of amenorrhea after treatment, but few data have been reported about the incidence of biochemical evidence for impaired ovarian function in patients who do not become overtly menopausal. METHODS: We conducted a cross-sectional study evaluating anti-Müllerian hormone (amh) in premenopausal chemotherapy-treated breast cancer survivors and control patients. Random serum levels of amh and other relevant clinical data were collected for 100 premenopausal chemotherapy-treated breast cancer survivors and 76 control subjects. Subgroup analyses were performed for women with regular menstrual cycles at the time of amh testing. RESULTS: After adjustment for age, amh was significantly lower in the overall group of patients receiving chemotherapy (p = 0.002) and in the subgroup reporting normal cycles (p = 0.03). Cyclophosphamide produced a significant dose-dependent reduction in amh (p < 0.001); trastuzumab was associated with increased amh in survivors with normal cycles. Overall, serum amh in survivors was roughly equivalent to that measured in control patients 12 years older. CONCLUSIONS: Young breast cancer survivors often experience significant impairment of ovarian function despite having normal menstrual cycles after treatment. Those results have important implications for patient counselling and the timing of possible referral to a fertility specialist.

Obesity-related health status is a better predictor of pregnancy with fertility treatment than body mass index: a prospective study.

This study assessed whether an obesity-related health status instrument (Edmonton obesity scoring system - EOSS) or body mass index (BMI) better predicted pregnancy rates in overweight women undergoing fertility treatments. A prospective cohort study was conducted on patients with a BMI ≥ 25 kg m(-2) undergoing a fertility treatment cycle (ovulation induction, superovulation, or in vitro fertilization). Obesity-related health status including blood pressure, blood work, health history, and functional assessment were assessed. A total of 101 patients were included in the study with an average age of 36.3 ± 4.2 years and a mean BMI of 31.8 ± 5.2 kg m(-2) . EOSS was found to be statistically predictive of pregnancy rate/cycle (OR 0.51, 95% CI 0.27-0.94; P = 0.03), whereas BMI was not (OR 0.95, 95% CI 0.86-1.05). A similar trend was seen for clinical pregnancy rate/cycle started. However, the association between clinical pregnancy rates and EOSS or BMI did not reach statistical significance (OR 0.53, P = 0.06 and OR 0.98, P = 0.62 respectively). Our results demonstrated that EOSS better predicted pregnancy rates after fertility treatments than BMI. In fact, for every EOSS stage increased by one unit, the odds of pregnancy were approximately halved. A multi-centre study powered for live birth is warranted to establish effective pre-fertility management of overweight women.

Correction of hyperandrogenemia by laparoscopic ovarian cautery in women with polycystic ovarian syndrome is not accompanied by improved insulin sensitivity or lipid-lipoprotein levels.

Polycystic ovarian syndrome (PCOS) is a common disorder associated with hyperandrogenemia and infertility. Abdominal obesity, insulin resistance, and dyslipoproteinemias are other common metabolic disorders typically found in women with PCOS. The cause-effect relationship between hyperandrogenemia and insulin resistance-dyslipoproteinemia remains unclear. In this study, we have investigated the changes in androgenemia, insulin sensitivity, and plasma lipid-lipoprotein levels after laparoscopic ovarian cautery (LOC) for ovulation induction in eight infertile women with clomiphene citrate-resistant PCOS. After LOC, significant decreases in androstenedione (43%), testosterone (48%), and free testosterone (48%) concentrations were observed (P < 0.05). Glucose utilization during an euglycemic-hyperinsulinemic clamp did not change after LOC. In addition, no significant changes after the surgical procedure were observed for cholesterol, triglycerides, and apolipoprotein concentrations measured in total plasma and in different lipoprotein fractions. In conclusion, within the short duration of observation of this study, our findings demonstrate that insulin resistance and lipoprotein abnormalities associated with PCOS are not secondary to hyperandrogenemia. The clinician, therefore, must be cognizant of the persistence of these metabolic risk factors for cardiovascular disease once successful ovulation and fertility is restored, and institute appropriate monitoring, counseling, and medical intervention as required.

Adhesion formation after laparoscopic ovarian cautery for polycystic ovarian syndrome: lack of correlation with pregnancy rate.

OBJECTIVE: To assess adhesion formation after laparoscopic ovarian cautery in women with polycystic ovarian syndrome (PCOS) and the efficacy of Interceed Adhesion Barrier (Ethicon, Summerville, NJ) in their prevention. DESIGN: Prospective, randomized, blinded, clinical study of laparoscopic ovarian cautery with application of Interceed to one ovary, followed by short interval second-look laparoscopy, scoring of adhesions, and clinical follow-up. SETTING: Tertiary care clinic at a University teaching hospital. PATIENTS: Eight infertile women with PCOS who failed to conceive with previous clomiphene citrate (CC) therapy. RESULTS: Periovarian adhesions of varying severity developed in all women after laparoscopic ovarian cautery. Interceed showed no protective effect. Despite this finding, all women initiated regular menses after laparoscopic ovarian cautery and seven of eight women spontaneously conceived eight singleton pregnancies without any further therapy. CONCLUSION: Laparoscopic ovarian cautery should be considered in infertile women with PCOS who fail to respond to CC therapy. These women must be counseled with respect to the possible complication of postoperative adhesion formation.

In vitro fertilization outcome in the presence of severe male factor infertility.

OBJECTIVE: To assess the outcome of standard IVF treatment (nonmicromanipulated) with respect to total motile sperm number recovered by swim-up, particularly for couples with severe male factor infertility defined as total motile sperm number < 0.5 x 10(6). DESIGN: Retrospective study of patients who underwent successful oocyte retrieval in an IVF program from August 10, 1992 to December 31, 1993. SETTING: A university-based tertiary referral center (The Toronto Hospital). PATIENTS: All cycles (n = 672) were divided into four groups according to total motile sperm number recovered using standard swim-up: group 1, total motile sperm number < or = 0.50 x 10(6); group 2, total motile sperm number between 0.51 and 1.00 x 10(6); group 3, total motile sperm number between 1.01 and 1.50 x 10(6); and group 4, total motile sperm number > or = 1.51 x 10(6). All patients received the same controlled ovarian hyperstimulation protocol, which consisted of a GnRH analog flare-up followed by parenteral menotropins. Clinical and cycle characteristics in the four groups were analyzed and outcome was evaluated. RESULTS: There was no significant difference in clinical and cycle characteristics between the groups. The uniformity of the groups justified analysis of their outcome. A fertilization rate of 21.5% was achieved in couples with severe male factor (group 1). Fertilization rate and number of embryos transferred increased directly with the total motile sperm number. There was no significant difference in implantation rate per embryo between the groups. CONCLUSIONS: The results in couples with severe male factor infertility compare favorably with monospermic fertilization rates reported in the literature using partial zona dissection and subzonal insertion but is lower than with intracytoplasmic sperm injection. Therefore, we believe that couples with severe male factor infertility should be considered for standard IVF, as long as adequate total motile sperm can be recovered (100 x 10(3) per dish). If intracytoplasmic sperm injection is available, it should be offered to these couples.

Type of stimulation protocol affects oocyte maturity, fertilization rate, and cleavage rate after intracytoplasmic sperm injection.

OBJECTIVE: To compare oocyte maturity, fertilization rate and cleavage rate after a short and long GnRH agonist (GnRH-a) stimulation protocol and intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective study of 34 sequential ICSI cycles stimulated with a short or long GnRH-a protocol. SETTING: A university-based tertiary care center for assisted reproductive treatment. RESULTS: Significantly more oocytes were mature (metaphase II) after a long GnRH-a protocol then after a short GnRH-a protocol (25.6% and 80.8%, respectively). The long protocol resulted in more cleaving embryos (36/152 versus 9/132) and more cycles of ET (12/17 versus 5/17) than the short group. CONCLUSION: A greater percentage of mature oocytes results from ovarian stimulation with a long GnRH-a protocol than a short GnRH-a protocol. Maturity could be assessed accurately after cumulus stripping that is required before ICSI. Fertilization rate and cleavage rate with ICSI was superior after a long GnRH-a stimulation protocol for superovulation.

The choice of embryo transfer catheter affects embryo implantation after IVF.

OBJECTIVE: Comparison of two transfer catheters in an IVF program. DESIGN: Prospective, randomized clinical study. SETTING: A private tertiary care center for ART. PATIENT(S): 66 patients < 38 years of age undergoing IVF and/or ICSI. INTERVENTION(S): Patients were randomly assigned to undergo ET using the Tomcat catheter (n = 32) or the TDT catheter (n = 34). MAIN OUTCOME MEASURE(S): Primary outcome measures were implantation and pregnancy rates. Secondary outcome measures were contamination with blood and/or mucus on the tip of the catheter, cramping or patient discomfort, and time required to complete ET. RESULT(S): Use of the Tomcat catheter resulted in significantly higher implantation (25.2% vs. 8.4%) and clinical pregnancy rates (47% vs. 14.7%) compared with the TDT catheter. All secondary outcome measures were similar for both catheters. CONCLUSION(S): The choice of ET catheter may affect the success of IVF-ET cycles. Use of the Tomcat catheter compared with the TDT catheter seems to result in significantly better efficiency of the ET procedure and is more cost effective.

Pulsatile release patterns of luteinizing hormone and progesterone in relation to symptom onset in women with premenstrual syndrome.

OBJECTIVE: To explore the pulsatile-release characteristics of LH and P in women with premenstrual syndrome (PMS) compared with age-matched phase-matched controls. DESIGN: Prospective, repeated measures, two-group study. SETTING: Human volunteers in an academic research environment. PARTICIPANTS: Six women with rigorously defined prospectively determined PMS; six age-matched phase-matched controls. MAIN OUTCOME MEASURES: Frequency, amplitude, concentration, and coincident pulsatile release characteristics of LH and P at three symptom-related points of the luteal phase. RESULTS: No significant between-group differences in frequency, amplitude, or concentration were found. In pooled data, significant coincident pulsing between LH and P was demonstrated. The length of time between LH and P pulses systematically increased across the luteal phase, a finding not previously reported. In the PMS group only, significant coincident pulsing occurred at an unexpected zero time lag on the symptom-onset sampling day. CONCLUSION: A progressively increasing coupling interval may reflect the gradual decline of the corpus luteum. Presence of a zero time lag between LH and P at symptom onset in women with PMS may indicate an aberrance in corpus luteum response to LH stimulation.

Laparoscopic ovarian cautery for polycystic ovarian syndrome.

Approximately 15% of all couples suffer from infertility, and in 10% of cases, anovulation or oligoovulation is a factor. One of the most common clinical syndromes in which anovulation occurs, often presenting as infertility, is the polycystic ovary syndrome (PCOS).

Recurrent maternal virilization during pregnancy associated with polycystic ovarian syndrome: a case report and review of the literature.

Maternal virilization in pregnancy is associated, in most benign cases, with luteoma of pregnancy and hyperreactio luteinalis. Only a few reports relate this phenomenon to hyperthecosis or polycystic ovarian syndrome (PCOS). A case of recurrent maternal virilization during two consecutive pregnancies in a patient with PCOS is presented. In both pregnancies, the deepening of her voice, facial hirsutism and scalp hair loss began at the end of the first trimester and regressed 3-4 months post-partum. The patient underwent ovarian venous catheterization, and androgen secretion from both ovaries was found to be markedly high but similar, therefore ruling out an ovarian androgen-secreting tumour. Reviewing the English literature of similar cases, we found reports of only seven cases of maternal virilization during pregnancy associated with PCOS. Here, we present a case of recurrent maternal virilization in pregnancy associated with PCOS.

In vitro fertilization programmed for weekday-only oocyte harvest: analysis of outcome based on actual retrieval day.

OBJECTIVE: Our aim was to assess the effect of the day of ovum retrieval on outcome in an IVF program scheduled for weekday-only ovum retrievals. DESIGN: This was a retrospective study of patients who underwent transvaginal ultrasound-guided ovum retrieval (TVUS-OR) in an IVF program from August 10, 1992, to April 30, 1993. SETTING: A university-based tertiary referral hospital center was the setting. PARTICIPANTS AND METHODS: All patients (n = 501) who underwent TVUS-OR were divided into three groups: (1) patients who underwent TVUS-OR on Monday; (2) patients who underwent retrieval on Tuesday, Wednesday, or Thursday; and (3) patients who underwent retrieval on Friday. All patients were induced by the same controlled ovarian hyperstimulation protocol, which consisted of a GnRH analogue "flare-up" followed by parenteral menotropins, after a scheduled oral contraceptive-induced menses. Patients and cycle characteristics in the three groups were compared and clinical outcome was evaluated. RESULTS: The similarity of patients and cycle characteristics confirmed the uniformity of the three groups. No difference was found in any of the clinical outcomes. However, in the first half of the program, we revealed a trend in which patients at high risk for ovarian hyperstimulation syndrome, requiring freezing all embryos and not allowing transfer during the treatment cycle, occurred more commonly in women whose retrieval occurred on Monday. This trend disappeared in the second half of the analysis. CONCLUSIONS: In an in vitro fertilization program in which ovum retrievals occurred only on weekdays, no significant difference in outcome was found in patients undergoing ovum retrieval on Monday or Friday versus midweek. In addition to significant savings by eliminating weekend retrievals, IVF outcome is not compromised.

Fertility-sparing surgery, with subsequent pregnancy, in persistent gestational trophoblastic neoplasia: case report.

Gestational trophoblastic neoplasia (GTN) is primarily a disease of women of reproductive age. In most instances, it is cured by surgical evacuation of the uterus, with persistent disease being very sensitive to chemotherapy. Hysterectomy, recommended for persistent chemotherapy-resistant uterine disease, may be unacceptable to the woman who wishes to maintain her fertility. Uterine resection of localized disease, with uterine reconstruction, may be a viable alternative. A case is presented of a woman with persistent uterine GTN, treated with localized uterine resection and reconstruction, followed by two successful pregnancies and deliveries. The literature is reviewed and potential pregnancy complications of this management, particularly uterine rupture, are discussed.

Successful twin pregnancy in a dual-transplant couple resulting from in-vitro fertilization and intracytoplasmic sperm injection: case report.

There are numerous reports of successful pregnancy following liver transplantation. Little information is available regarding the incidence and management of infertility in transplant recipients, particularly the use of artificial reproductive technologies. We present a case of a successful twin pregnancy resulting from in-vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI) in a liver transplant recipient, whose partner was a renal transplant recipient with severe oligozoospermia. With careful evaluation and monitoring, and the involvement of appropriate consultants, artificial reproductive technologies can be safely used in transplant recipient couples experiencing infertility.

Preliminary experience with subcutaneous human ovarian cortex transplantation in the NOD-SCID mouse.

Xenogeneic transplantation of ovarian cortex into an immunodeficient animal host may be an approach toward fertility preservation for young female patients undergoing cancer therapy. Our objective was to evaluate the development of follicles in human ovarian cortex placed s.c. in non-obese diabetic-severe combined immune deficiency (NOD-SCID) mice (n = 54). The following variables were compared: 1) male versus female mice as hosts, 2) intact versus pituitary down-regulated mice, and 3) warm versus cold tissue transport. After 2 wk, 37 of 50 (74%) of the human xenografts contained follicles. At 12 wk after transplantation, exogenous gonadotropin stimulation resulted in follicle growth in 19 of 37 (51%) of the grafts, including the development of antral follicles, which could be palpated and visualized through the mouse skin. Significantly more developing follicles were identified in male versus female mice (13 of 17 vs. 6 of 20, respectively; p = 0.013) after stimulation. No difference was found between intact and pituitary down-regulated mice as hosts. Follicular survival was significantly increased by warm versus cold tissue transport. Our results suggest that s.c. ovarian cortex xenografting into NOD-SCID mice is feasible. Primordial follicles in ovarian xenografts retain their developmental potential and form antral follicles following gonadotropin stimulation.