Does ovarian stimulation regimen affect IVF outcome? a two-centre, real-world retrospective study using predominantly cleavage-stage, single embryo transfer.

In this study, ovarian stimulation using highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) for IVF were compared in two large assisted reproduction technique centres in Sweden. A total of 5902 women underwent 9631 oocyte retrievals leading to 8818 embryo transfers (7720 on day 2): single embryo transfers (74.2%); birth rate per embryo transfer (27.7%); multiple birth rate (5.0%); incidence of severe ovarian hyperstimulation syndrome (0.71%). Compared with ovarian stimulation with rFSH, women who received HP-HMG were older, had higher dosages of gonadotrophins administered, fewer oocytes retrieved and more embryos transferred. After multivariate analysis controlling for age and generalized estimating equation model, no differences were found in delivery outcomes per embryo transfers between HP-HMG and rFSH, independent of gonadotrophin releasing hormone analogue (GnRH) used. Logit curves for live birth rate suggested differences for various subgroups, most prominently for women with high oocyte yield or when high total doses were used. Differences were not significant, perhaps owing to skewed distributions of the FSH compounds versus age and other covariates. These 'real-life patients' had no differences in live birth rate between HP-HMG and rFSH overall or in subgroups of age, embryo score, ovarian sensitivity or use of GnRH analogue regimen.

Weight reduction intervention for obese infertile women prior to IVF: a randomized controlled trial.

STUDY QUESTION: Does an intensive weight reduction programme prior to IVF increase live birth rates for infertile obese women? SUMMARY ANSWER: An intensive weight reduction programme resulted in a large weight loss but did not substantially affect live birth rates in obese women scheduled for IVF. WHAT IS ALREADY KNOWN: Among obese women, fertility and obstetric outcomes are influenced negatively with increased risk of miscarriage and a higher risk of maternal and neonatal complications. A recent large randomized controlled trial found no effect of lifestyle intervention on live birth in infertile obese women. STUDY DESIGN, SIZE, DURATION: A prospective, multicentre, randomized controlled trial was performed between 2010 and 2016 in the Nordic countries. In total, 962 women were assessed for eligibility and 317 women were randomized. Computerized randomization with concealed allocation was performed in the proportions 1:1 to one of two groups: weight reduction intervention followed by IVF-treatment or IVF-treatment only. One cycle per patient was included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Nine infertility clinics in Sweden, Denmark and Iceland participated. Women under 38 years of age planning IVF, and having a BMI ≥30 and <35 kg/m2 were randomized to two groups: an intervention group (160 patients) with weight reduction before IVF, starting with 12 weeks of a low calorie liquid formula diet (LCD) of 880 kcal/day and thereafter weight stabilization for 2-5 weeks, or a control group (157 patients) with IVF only. MAIN RESULTS AND ROLE OF CHANCE: In the full analysis set (FAS), the live birth rate was 29.6% (45/152) in the weight reduction and IVF group and 27.5% (42/153) in the IVF only group. The difference was not statistically significant (difference 2.2%, 95% CI: 12.9 to -8.6, P = 0.77). The mean weight change was -9.44 (6.57) kg in the weight reduction and IVF group as compared to +1.19 (1.95) kg in the IVF only group, being highly significant (P < 0.0001). Significantly more live births were achieved through spontaneous pregnancies in the weight reduction and IVF group, 10.5% (16) as compared to the IVF only group 2.6% (4) (P = 0.009). Miscarriage rates and gonadotropin dose used for IVF stimulation did not differ between groups. Two subgroup analyses were performed. The first compared women with PCOS in the two randomized groups, and the second compared women in the weight reduction group reaching BMI ≤ 25 kg/m2 or reaching a weight loss of at least five BMI units to the IVF only group. No statistical differences in live birth rates between the groups in either subgroup analysis were found. LIMITATIONS, REASON FOR CAUTION: The study was not powered to detect a small increase in live births due to weight reduction and was not blinded for the patients or physician. Further, the intervention group had a longer time to achieve a spontaneous pregnancy, but were therefore slightly older than the control group at IVF. The study only included women with a BMI lower than 35 kg/m2. WIDER IMPLICATIONS OF THE FINDINGS: The study suggests that weight loss for obese women (BMI: 30-34.9 kg/m2) may not rectify the outcome in IVF cycles, although a significant higher number of spontaneous conceptions occurred in the weight loss group. Also, the study suggests that intensive weight reduction with LCD treatment does not negatively affects the results. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Sahlgrenska University Hospital (ALFGBG-70 940), Merck AB, Solna, Sweden (an affiliate of Merck KGaA, Darmstadt, Germany), Impolin AB, Hjalmar Svensson Foundation and Jane and Dan Olsson Foundation. Dr Thurin-Kjellberg reports grants from Merck, non-financial support from Impolin AB, during the conduct of the study, and personal fees from Merck outside the submitted work. Dr Friberg reports personal fees from Ferring, Merck, MSD, Finox and personal fees from Studentlitteratur, outside the submitted work. Dr Englund reports personal fees from Ferring, and non-financial support from Merck, outside the submitted work. Dr Bergh reports and has been reimbursed for: writing a newsletter twice a year (Ferring), lectures (Ferring, MSD, Merck), and Nordic working group meetings (Finox). Dr Karlström reports lectures (Ferring, Finox, Merck, MSD) and Nordic working group meetings (Ferring). Ms Kluge, Dr Einarsson, Dr Pinborg, Dr Klajnbard, Dr Stenlöf, Dr Larsson, Dr Loft and Dr Wistrand have nothing to disclose. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT01566929. TRIAL REGISTRATION DATE: 23-03-2012. DATE OF FIRST PATIENT'S ENROLMENT: 05-10-2010.

Full-term newborn after repeated ovarian tissue transplants in a patient treated for Ewing sarcoma by sterilizing pelvic irradiation and chemotherapy.

We report the first successful transplantation of cryopreserved ovarian cortical tissue into heavily irradiated tissues in a patient who had received sterilizing pelvic radiotherapy (54 Gy) and 40 weeks of intensive high-dose chemotherapy for the treatment of Ewing's sarcoma 14 years earlier. Repeated transplantation procedures were required to obtain fully functional follicular development. Enlargement of the transplants over time and increase of the size of the uterus were demonstrated on sequential ultrasonographic examinations. Eggs of good quality that could be fertilized in vitro were obtained only after a substantial incremental increase of the amount of ovarian tissue transplanted. Single embryo replacement resulted in a normal pregnancy and the birth of a healthy child by cesarean section at full-term. No neonatal or maternal postoperative complications occurred. Women facing high-dose pelvic radiotherapy should not be systematically excluded from fertility preservation options, as is currently the trend.

Gamete donors' satisfaction; gender differences and similarities among oocyte and sperm donors in a national sample.

OBJECTIVE: To explore oocyte and sperm donors' emotional stress, experiences of care and satisfaction after donation. DESIGN: Prospective multicenter study. SETTINGS: All fertility clinics performing gamete donation in Sweden during the period 2005 to 2008. POPULATION: Of 220 eligible oocyte donors who were approached, 181 agreed to complete the first questionnaire and 165 completed the second questionnaire 2 months after oocyte donation. Of 156 eligible sperm donors 119 accepted to complete the first questionnaire before donation. Eighty-nine participants completed the second questionnaire 2 months after sperm donation. METHODS: Standardized and study-specific questionnaires. MAIN OUTCOME MEASURES: Satisfaction with the donation, respondents' mental health and overall care. RESULTS: A larger percentage of sperm donors (97.8%) were satisfied with their overall experience of being a donor than oocyte donors (85.9%, p = 0.003). Some oocyte and sperm donors did not receive sufficient information about practical issues (9.1% and 13.5%, respectively) and future consequences (12.8% and 3.4%, respectively, p = 0.014). The donors' symptoms of anxiety and depression did not show any differences in relation to negative or positive perceptions of satisfaction. The donors who did not indicate ambivalence before treatment were on average almost five times more satisfied compared with those who did indicate ambivalence (odds ratio 4.71; 95% CI 1.34-16.51). CONCLUSIONS: Most donors were satisfied with their contribution after the donation. Oocyte and sperm donors who expressed ambivalence before donation were less satisfied after donation. In vitro fertilization staff fulfilled most of the donors' needs for information and care.

Gamete donors' motivation in a Swedish national sample: is there any ambivalence? A descriptive study.

OBJECTIVE: To study donors' motivation and ambivalence before donation of gametes. DESIGN: Cross-sectional study. SETTING: Seven Swedish university hospital clinics. Sample. Of the 220 eligible oocyte donors and 156 eligible sperm donors who were approached, 181 (82%) oocyte donors and 119 (76%) sperm donors agreed to participate. METHODS: Gamete donors completed a questionnaire in the clinic prior to the donation. MAIN OUTCOME MEASURES: Motives and ambivalence towards donation. RESULTS: In general, gamete donors donated for altruistic reasons (95%). A greater percentage of oocyte than sperm donors had a personal experience of biological children, which motivated them to donate (65 vs. 32%). A greater percentage of sperm donors compared with oocyte donors were curious about their own fertility (24 vs. 9%), and they also believed that they were contributing what they regarded as their own good genes to other couples (45 vs. 20%). Prior to donation, potential sperm donors were more ambivalent towards donating than were oocyte donors (39 and 21%, p < 0.001). CONCLUSIONS: The motives to donate gametes are mainly altruistic. We conclude that men and women differ in their view towards donating gametes. Sperm donors had a higher degree of ambivalent feelings towards donation than oocyte donors.

Alterations in the expression, structure and function of progesterone receptor membrane component-1 (PGRMC1) in premature ovarian failure.

Premature ovarian failure (POF) is characterized by hypergonadotropic hypogonadism and amenorrhea before the age of 40. The condition has a heterogeneous background but genetic factors are demonstrated by the occurrence of familial cases. We identified a mother and daughter with POF both of whom carry an X;autosome translocation [t(X;11)(q24;q13)]. RNA expression studies of genes flanking the X-chromosome breakpoint revealed that both patients have reduced expression levels of the gene Progesterone Receptor Membrane Component-1 (PGRMC1). Mutation screening of 67 females with idiopathic POF identified a third patient with a missense mutation (H165R) located in the cytochrome b5 domain of PGRMC1. PGRMC1 mediates the anti-apoptotic action of progesterone in ovarian cells and it acts as a positive regulator of several cytochrome P450 (CYP)-catalyzed reactions. The CYPs are critical for intracellular sterol metabolism, including biosynthesis of steroid hormones. We show that the H165R mutation associated with POF abolishes the binding of cytochrome P450 7A1 (CYP7A1) to PGRMC1. In addition, the missense mutation attenuates PGRMC1's ability to mediate the anti-apoptotic action of progesterone in ovarian cells. These findings suggest that mutant or reduced levels of PGMRC1 may cause POF through impaired activation of the microsomal cytochrome P450 and increased apoptosis of ovarian cells.

Down-regulation of progesterone receptor membrane component 1 (PGRMC1) in peripheral nucleated blood cells associated with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS).

BACKGROUND: Progesterone receptor membrane component 1 (PGRMC1) is a member of a progesterone-binding complex implicated in female reproduction. We aimed i) to determine the natural expression of PGRMC1 in peripheral nucleated blood cells throughout the menstrual cycle and ii) to investigate any association between PGRMC1 levels in leukocytes and conditions characterized by reduced fertility. METHODS: We analyzed PGRMC1 expression in peripheral leukocytes from 15 healthy cycling women over four weeks. Additionally, we determined PGRMC1 levels in samples from patients with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS) as well as in healthy postmenopausal women and male controls. The levels of PGRMC1 protein in nucleated peripheral blood cells were quantified by Western blot analysis. RESULTS: PGRMC1 levels did not vary significantly throughout the menstrual cycle. We observed a significant down-regulation of PGRMC1 in postmenopausal women and in patients with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS) when compared to early follicular phase of healthy women. CONCLUSION: This study suggests that reduced levels of PGRMC1 in peripheral leukocytes are associated with perturbed ovulatory function.

Hyaluronan-enriched transfer medium in cleavage-stage frozen-thawed embryo transfers increases implantation rate without improvement of delivery rate.

OBJECTIVE: To investigate the efficacy of hyaluronan-enriched transfer media in cleavage-stage frozen embryo transfer cycles. DESIGN: Two commercially available transfer media were prospectively compared in an observational study. SETTING: Hospital-based in vitro fertilization clinic. PATIENT(S): Patients (n = 425) undergoing frozen-thawed embryo transfer (FET). The embryos transferred were included in either a study group (high hyaluronic acid [HA], n = 199) or a control group (low HA, n = 226). INTERVENTION(S): Delivery rate per FET; positive hCG rate, biochemical pregnancy rate, clinical pregnancy rate, implantation rate, and clinical abortion rate were secondary outcomes. RESULT(S): The use of HA in the transfer media significantly increased the positive hCG rate (37.2% vs. 25.2%) and implantation rate (23.1% vs. 15.8%) without increasing the delivery rate (21.6% vs. 21.2%). More subjects in the study group with a positive hCG test experienced biochemical pregnancy (28.4% vs. 8.9%). CONCLUSION(S): Addition of HA to transfer media seems to favor attachment of early embryos in FETs without increasing the delivery rate.

Female university students' attitudes to future motherhood and their understanding about fertility.

OBJECTIVES: As highly educated women tend to postpone childbearing, the purpose was to explore female university students' attitudes to future motherhood and their understanding about fertility. METHODS: Female students (n = 300), visiting a Student Health Centre in Sweden, answered a questionnaire with mainly multiple choice questions and verbal rating scales. RESULTS: The women wanted to have two to three children at the age of 29 for the first birth and 35 for the last. Only 2.7% did not plan to have any children. Six out of 10 would consider having an abortion if confronted with an unplanned pregnancy 'right now'. The most important circumstances for women's decision to have children were to be sufficiently mature, have a stable partner to share parenthood with, have completed studies and have a good economy. Having children before they got 'too old' was only ranked as very important by 18% of women. The women had an acceptable understanding about fertility. CONCLUSIONS: It appears that female university students are not very concerned about having children before they get 'too old'. Therefore, it is important that caregivers, working with contraceptive counselling also include information about fertility, especially to women who intend to postpone their motherhood.