Planned oocyte cryopreservation: a systematic review and meta-regression analysis.

BACKGROUND: Awareness of the age-related decline in fertility potential has increased the popularity of planned oocyte cryopreservation (POC). However, data regarding outcomes of POC, including rates of women returning to thaw oocytes, as well as pregnancy and live birth rates, are scarce and based mostly on small case series. OBJECTIVE AND RATIONALE: POC was defined as cryopreservation exclusively for prevention of future age-related fertility loss. The primary outcome was live birth rate per patient. The secondary outcomes included the return to thaw rate and laboratory outcomes. A meta-regression analysis examining the association between live birth and age above 40 or below 35 was conducted. SEARCH METHODS: We conducted a systematic database search from inception to August 2022. The search included PubMed (MEDLINE) and EMBASE. Our search strategies employed a combination of index terms (Mesh) and free text words to compile relevant concepts. The systematic review and meta-regression were undertaken following registration of systematic review (PROSPERO registration number CRD42022361791) and were reported following guidelines of Preferred Reporting Items for Systematic Review and Meta-Analyses 2020 (PRISMA 2020). OUTCOMES: The database search yielded 3847 records. After the selection process, 10 studies, conducted from 1999 to 2020, were included. Overall, 8750 women underwent POC, with a mean cryopreservation age of 37.2 (±0.8). Of those, 1517 women returned to use their oocytes with a return rate of 11.1% (± 4.7%). The mean age at the time of cryopreservation for women who returned to use their oocytes was 38.1 (±0.4), with an average of 12.6 (±3.6) cryopreserved oocytes per woman. In a meta-analysis, the oocyte survival rate was 78.5% with a 95% CI of 0.74-0.83 (I2 = 93%). The live birth rate per patient was 28% with a 95% CI of 0.24-0.33 (I2 = 92%). Overall, 447 live births were reported. In a sub-group analysis, women who underwent cryopreservation at age ≥40 achieved a live birth rate per patient of 19% (95% CI 0.13-0.29, I2 = 6%), while women aged ≤35 years old or younger had a higher live birth rate per patient of 52% (95% CI 0.41-0.63, I2 = 7%). WIDER IMPLICATIONS: POC emerges as a feasible option for women aiming to improve their chances of conceiving at a later reproductive age. Nonetheless, it must be acknowledged that the overall success rates of POC are limited and that the likelihood of successful live birth declines as the age at cryopreservation rises. With increasing interest in POC, the collation of comprehensive and high-quality data is imperative to clearly define the outcomes for various age groups. REGISTRATION NUMBER: CRD42022361791.

What are the most common controversial clinical issues in fertility preservation? A content analysis of a collaborative professional online consultation group.

RESEARCH QUESTION: Clinicians involved in fertility preservation (FP) are often required to make prompt and consequential decisions despite the absence of evidence-based data. We established a collaborative professional online consultation group for fertility preservation issues. We sought to determine the main controversial clinical issues in FP as raised by participants of this group. DESIGN: Content analysis of a dedicated community of practice interacting via a messaging application (WhatsApp) and a survey of group participants. RESULTS: Between January 2019 and July 2022, group members posed 39 clinical questions which were discussed and debated by the group. Common themes included management of oncofertility cases (33%), potential gonadotoxicity of various therapies (23%), fertility preservation in women and girls with premature ovarian insufficiency (POI) (18%), and technical aspects of ovarian tissue cryopreservation (10%). All but one query received prompt response (mean time for first response for 95% of queries 7.1 ± 9.0 min) from a mean of 5.4 ± 3.2 members. An anonymous online survey of group members was conducted during August 2022 (n = 31, response rate 94%). The majority of respondents stated they gained knowledge and assistance in clinical decision making from participation in the discussion group (90% and 58% of respondents, respectively). CONCLUSIONS: Management of clinical oncofertility cases, potential gonadotoxic effect of therapeutics and fertility preservation in women and girls with POI were the most common controversial issues in our fertility preservation community of practice. Intra-professional collaborative communication via a messaging application can aid in clinical management of fertility preservation and augment clinician's knowledge.

Clinical outcome of planned oocyte cryopreservation at advanced age.

PURPOSE: To report outcome of planned oocyte cryopreservation (POC) in the first 8 years of this treatment in our center. METHODS: A retrospective study in a university-affiliated medical center. RESULTS: A total of 446 women underwent POC during 2011-2018. Fifty-seven (13%) women presented to use these oocytes during the study period (until June 2021). POC was performed at a mean age of 37.9 ± 2.0 (range 33-41). Age at thawing was 43.3 ± 2.1 (range 38-49). A total of 34 (60%) women transferred their oocytes for thawing at other units. Oocyte survival after thawing was significantly higher at our center than following shipping to ancillary sites (78 vs. 63%, p = 0.047). Forty-nine women completed their treatment, either depleting their cryopreserved oocytes without conceiving (36) or attaining a live birth (13)-27% live birth rate per woman. Only one of eleven women who cryopreserved oocytes aged 40 and older had a live birth using thawed oocytes. CONCLUSION: Women should be advised to complete planned oocyte cryopreservation before age 40, given low success rates in women who underwent cryopreservation at advanced reproductive age. In this study, oocyte shipping was associated with lower survival rate. These findings may be relevant for women considering POC and utilization of cryopreserved oocytes.

The association between primary cesarean delivery in primipara and subsequent mode of conception, a retrospective study.

OBJECTIVE: To examine the association between primary cesarean delivery and the mode of conception in the subsequent delivery among women without a history of infertility. METHODS: A retrospective study. Women with the first two consecutive deliveries in our medical center were included. Excluded were women who conceived following fertility treatments or were older than 35 years at their first delivery. RESULTS: Twenty-three thousand four hundred and twenty-seven women were included in the study. Of those, 2215 (9.5%) underwent cesarean delivery in their first delivery, while 21,212 (90.5%) delivered vaginally. Univariate analysis revealed that women with primary cesarean delivery compared to women how delivered vaginally had higher rates of fertility treatments at the subsequent delivery (2.5 vs. 0.8%; p < .01). Those who had fertility treatments were significantly older during both the first and second deliveries, had higher rates of diabetic disorders of pregnancy (pregestational and gestational) at both the first and second deliveries, obesity and morbid obesity at the second delivery, and higher incidence of repeat cesarean delivery. Multivariate analysis revealed that the only factor that correlated significantly with the use of fertility treatments at the second delivery was maternal age at second delivery [aOR 1.2 (1.1-1.3), p < .01]. CONCLUSION: Among women without a history of infertility, cesarean delivery in the first delivery is not independently associated with fertility treatments in the subsequent delivery.

'Luckily, I don't believe in statistics': survey of women's understanding of chance of success with futile fertility treatments.

RESEARCH QUESTION: Why are women who face poor prognoses for success in assisted reproductive technology (ART) treatment choosing to pursue procedures using their own eggs, despite receiving information that their chances of success are very low. DESIGN: Cross-sectional study based on an anonymous questionnaire distributed to women aged between 43 and 45 years, undergoing ART using their own oocytes, at six public outpatient fertility clinics and three public in-hospital IVF units in Israel between 2015 and 2016. The main outcome measure was personal estimation of chance to achieve a live birth after the current ART treatment cycle and the cumulative estimated rate after all the treatment cycles the patient intended to undergo. RESULTS: Response rate was 70.0%, with 91 participants of mean age 43.8 ± 0.7 years. Participants estimated their delivery rates after the next ART treatment cycle at 49.0 ± 31.8% (response rate 93.4%) and their cumulative delivery rates after all the ART treatments they would undergo at 57.7 ± 36.3% (response rate 90.1%). This is significantly higher than the predicted success rates of 5% and 15%, respectively (both P < 0.001), which are based on national register data. Nearly one-half of patients rated themselves as having a better than average chance of conception (47.3%). CONCLUSION: Women do not pursue futile treatments because they lack information. Despite being informed of the low success rates of conception using ART treatments, many patients of advanced maternal age have unrealistically high expectations from ART, essentially ignoring their estimated prognosis when deciding on treatment continuation. Future work should examine the psychological reasons behind continuing futile fertility treatments.

Cancer in IVF patients treated at age 40 years and older: long term follow-up.

RESEARCH QUESTION: Current knowledge of cancer risk among women who undergo IVF is based mainly on studies of women treated in their thirties, frequently with short follow-up periods. Therefore, information about cancer risk among infertile menopausal women is limited. We aimed to evaluate the risk of cancer among IVF patients treated at age 40 years and older, followed up for an extended period. DESIGN: Historical cohort study of all IVF patients treated at the age of 40 years or older at two university-affiliated IVF units in Jerusalem, Israel, between 1994 and 2002. Data were cross-linked with the Israel National Cancer Registry to 2016. Standardized incidence ratios (SIR) and 95% confidence intervals were computed by comparing the observed number of cancer cases with the expected cancer rate in the general Israeli population adjusted for age and year of birth. In addition, Kaplan-Meier analysis was conducted to account for the length of follow-up. RESULTS: A total of 501 patients were included in the analysis, with mean follow-up of 16.7 ± 3.7 years (range 2-22 years). Mean age at first IVF cycle was 42.3 years (±2.1). Mean number of IVF cycles was 3.2 ± 2.6 (range 1-15). Thirty-six women (7.2%) developed invasive cancer, compared with 47.2 expected cases; SIR 0.76 (95% CI 0.53 to 1.06); 22 women were diagnosed with invasive breast cancer, compared with 19.84 expected; SIR 1.11 (95% CI 0.69 to 1.68). CONCLUSIONS: Older women undergoing IVF treatment were not significantly associated with an excess risk of cancer at long-term follow up. Further studies, however, are needed to confirm these findings.

Physician experience is associated with greater underestimation of patient pain.

OBJECTIVE: Procedural pain is unique in that physicians simultaneously cause and assess it. Experienced male physicians are known to underestimate their female patients' pain more than other physicians. However, it is unknown whether this also occurs in obstetrics/gynecology, where all patients are females. This study addresses the gap in literature on procedural pain assessment accuracy. METHODS: The present research compares paired pain evaluations from 20 obstetricians/gynecologists and their 92 female patients. RESULTS: Our data demonstrate that patients' reported pain levels (M = 5.53, SD = 2.7) were significantly higher than their physicians' pain estimates (M = 4.89, SD = 2.19), t = 2.64, p < 0.005. The gap between patients' and physicians' pain estimates was greatest among physicians with the greatest procedural experience (M = 1.49, SD = 2.24), f = 5.72, p < 0.005. Male physicians underestimated their patients' pain significantly more than female physicians do, t = 2.27, p < 0.05. CONCLUSION: Our results shed light on systematic underestimation of procedural pain and highlight the significance of experience and sex differences in pain evaluation. PRACTICE IMPLICATIONS: Physicians' experience influences their perception of patient pain while performing procedures. Experienced male physicians, even those who exclusively treat female patients, need to be aware of this ubiquitous bias in assessing their female patients' procedural pain.

Invasive Prenatal Diagnostic Testing Recommendations are Influenced by Maternal Age, Statistical Misconception and Perceived Liability.

Funding policy and medico-legal climate are part of physicians' reality and might permeate clinical decisions. This study evaluates the influence of maternal age and government funding on obstetrician/gynecologist recommendation for invasive prenatal testing (i.e. amniocentesis) for Down syndrome (DS), and its association with the physician's assessment of the risk of liability for medical malpractice unless they recommend amniocentesis. Israeli physicians (N = 171) completed a questionnaire and provided amniocentesis recommendations for women at 18 weeks gestation with normal preliminary screening results, identical except aged 28 and 37. Amniocentesis recommendations were reversed for the younger ('yes' regardless of testing results: 6.4%; 'no' regardless of testing results: 31.6%) versus older woman ('yes' regardless of testing results: 40.9%; 'no' regardless of testing results: 7.0%; χ2 = 71.55, p < .01). About half of the physicians endorsed different recommendations per scenario; of these, 65.6% recommended amniocentesis regardless of testing results for the 37-year-old woman. Physicians routinely performing amniocentesis and those advocating for amniocentesis for all women ≥ age 35 were approximately twice as likely to vary their recommendations per scenario. Physicians who perceived risk of liability for malpractice as large were nearly one-and-a-half times more likely to vary recommendations. The results indicate physicians' recommendations are influenced by maternal age, though age is already incorporated in prenatal DS risk evaluations. The physician's assessment of the risk that they will be sued unless they recommend amniocentesis may contribute to this spurious influence.

"A Phenomenal Person and Doctor": Thank You Letters to Medical Care Providers.

BACKGROUND: Thank you letters to physicians and medical facilities are an untapped resource, providing an invaluable glimpse into what patients notice and appreciate in their care. OBJECTIVE: The aim of this study was to analyze such thank you letters as posted on the Web by medical institutions to find what patients and families consider to be good care. In an age of patient-centered care, it is pivotal to see what metrics patients and families apply when assessing their care and whether they grasp specific versus general qualities in their care. METHODS: Our exploratory inquiry covered 100 thank you letters posted on the Web by 26 medical facilities in the United States and the United Kingdom. We systematically coded and descriptively presented the aspects of care that patients and their families thanked doctors and medical facilities for. We relied on previous work outlining patient priorities and satisfaction (Anderson et al, 2007), to which we added a distinction between global and specific evaluations for each of the already existing categories with two additional categories: general praise and other, and several subcategories, such as treatment outcome, to the category of medical care. RESULTS: In 73% of the letters (73/100), physicians were primarily thanked for their medical treatment. In 71% (71/100) of the letters, they were thanked for their personality and demeanor. In 52% cases (52/100), these two aspects were mentioned together, suggesting that from the perspective of patient as well as the family member, both are deemed necessary in positive evaluation of medical care. Only 8% (8/100) of the letters lacked reference to medical care, personality or demeanor, or communication. No statistically significant differences were observed in the number of letters that expressed gratitude for the personality or demeanor of medical care providers versus the quality of medical care (χ21, N=200=0.1, not statistically significant). Letters tended to express more specific praise for personality or demeanor, such as being supportive, understanding, humane and caring (48/71, 68%) but more general praise for medical care (χ21, N=424=63.9, P<.01). The most often mentioned specific quality of medical care were treatment outcomes (30/73, 41%), followed by technical competence (15/73, 21%) and treatment approach (14/73, 19%). A limitation of this inquiry is that we analyzed the letters that medical centers chose to post on the Web. These are not necessarily a representative sample of all thank you letters as are sent to health care institutions but are still indicative of what centers choose to showcase on the Web. CONCLUSIONS: Physician demeanor and quality of interaction with patients are pivotal in how laymen perceive good care, no less so than medical care per se. This inquiry can inform care providers and medical curricula, leading to an improvement in the perceived quality of care.

How Many Embryos should be Transferred? The Relevance of Parity and Obstetric History.

BACKGROUND: Fertility treatments are responsible for the rise in high order pregnancies in recent decades and their associated complications. Reducing the number of embryos returned to the uterus will reduce the rate of high order pregnancies. OBJECTIVES: To explore whether obstetric history and parity have a role in the clinician's decision making regarding the number of embryos transferred to the uterus during in vitro fertilization (IVF). METHODS: In a retrospective study for the period August 2005 to March 2012, data of twin deliveries > 24 weeks were collected, including parity, mode of conception (IVF vs. spontaneous), gestational age at delivery, preeclampsia, birth weight, admission to the neonatal intensive care unit (NICU), and Apgar scores. RESULTS: A total of 1651 twin deliveries > 24 weeks were record- ed, of which 959 (58%) were at term (> 37 weeks). The early preterm delivery (PTD) rate (< 32 weeks) was significantly lower with increased parity (12.6%, 8.5%, and 5.6%, in women with 0, 1, and ≥ 2 previous term deliveries, respectively). Risks for PTD (< 37 weeks), preeclampsia and NICU admission were significantly higher in primiparous women compared to those who had one or more previous term deliveries. Primiparity and preeclampsia, but not IVF, were significant risk factors for PTD. CONCLUSIONS: The risk for PTD in twin pregnancies is significantly lower in women who had a previous term delivery and decreases further after two or more previous term deliveries. This finding should be considered when deciding on the number of embryos to be transferred in IV.

Intrapartum fetal heart rate patterns of trisomy 21 fetuses: A case-control study.

BACKGROUND/AIM: To determine whether there are specific characteristic intrapartum heart rate patterns for fetuses with trisomy 21(T21). BACKGROUND STUDY DESIGN/PATIENTS: Intrapartum fetal heart rate (FHR) tracings of T21 fetuses were compared to those of euploid fetuses in a retrospective, observational, matched, case-control study. The study group consisted of 42 fetuses with T21 and 42 matched euploid controls. Matching was designed to accommodate possible confounders. The sign test and McNemar's test were used for categorical variables. The paired t test was used for comparison between quantitative variables. RESULTS: Intrapartum baseline FHR of fetuses with T21 was found to be slightly decreased compared to controls (122.5 vs 129.05 beats per minute, p=0.028). No differences were detected in the presence of periodic changes, or FHR variability between the groups. CONCLUSION: When evaluating intrapartum FHR of fetuses with T21, decreased baseline FHR can be expected.

Ovarian stimulation for oocyte cryopreservation for prevention of age-related fertility loss: one in five is a low responder.

Oocyte cryopreservation for age-related fertility loss is gaining interest considering the tendency to postpone motherhood in many societies. Little is currently known about the actual efficiency of this approach. We aimed to explore ovarian response of presumably fertile women undergoing in vitro fertilization for this indication. A total of 105 women underwent 151 stimulation cycles at mean age 37.7 ± 2.4. None had known infertility. Mean daily starting FSH dose was 371 ± 110 (225-600). Mean number of mature oocytes cryopreserved at the first completed cycle was 9.7 ± 7.5 (0-43). However, 21% of started cycles were either cancelled before egg retrieval or resulted in 0-3 mature oocytes retrieved. Therefore, women considering oocyte cryopreservation for prevention of age-related fertility decline should be encouraged to perform this procedure at younger age than, preferably before 35.

Preconception screening for cytomegalovirus: an effective preventive approach.

Congenital cytomegalovirus (CMV) is the leading infectious cause of sensorineural hearing loss and delayed psychomotor development. Viral transmission to the fetus is far more likely to occur following a primary than a secondary maternal infection. Primary prevention seems to be the best means to reduce the burden of congenital CMV due to the lack of treatment options during pregnancy. We evaluated this approach on a cohort of 500 women planning pregnancy who attended our fertility clinic. Of the 444 who underwent CMV screening, 18 (4.1%) had positive IgM serology for CMV; of these, IgG avidity was high in 12 (remote infection) and low in 6 (recent infection). The latter were advised to delay pregnancy. All women who were seroimmune for CMV (366/444, 82.4%), including the 12 with remote infection, continued fertility treatment. The remaining patients (72/444, 16.2%), who were not immune to CMV at the initial screen, were advised to minimize CMV exposure by improving personal hygiene and to continue fertility treatment. None of the 69/72 (95.8%) women who were followed for one year were infected with CMV. Cytomegalovirus testing and counselling at preconception seemed effective in reducing CMV exposure in pregnancy.

Physician recommendation for invasive prenatal testing: the case of the 'precious baby'.

STUDY QUESTION: Do clinicians manage pregnancies conceived by assisted reproductive technologies (ART) differently from spontaneous pregnancies? SUMMARY ANSWER: Clinicians' decisions about prenatal testing during pregnancy depend, at least partially, on the method of conception. WHAT IS KNOWN ALREADY: Research thus far has shown that patients' decisions regarding prenatal screening are different in ART pregnancies compared with spontaneous ones, such that ART pregnancies may be considered more valuable or 'precious' than pregnancies conceived without treatment. STUDY DESIGN, SIZE AND DURATION: In this cross-sectional study, preformed during the year 2011, 163 obstetricians and gynecologists in Israel completed an anonymous online questionnaire. PARTICIPANTS, SETTING, METHODS: Clinicians were randomly assigned to read one of two versions of a vignette describing the case of a pregnant woman. The two versions differed only with regard to the method of conception (ART; n = 78 versus spontaneous; n = 85). Clinicians were asked to provide their recommendations regarding amniocentesis. MAIN RESULTS AND THE ROLE OF CHANCE: The response rate among all clinicians invited to complete the questionnaire was 16.7%. Of the 85 clinicians presented with the spontaneous pregnancy scenario, 37 (43.5%) recommended amniocentesis. In contrast, of the 78 clinicians presented with the ART pregnancy scenario, only 15 (19.2%) recommended the test. Clinicians were 3.2 (95% confidence interval [CI]: 1.6-6.6) times more likely to recommend amniocentesis for a spontaneous pregnancy than for an ART pregnancy. LIMITATIONS AND REASONS FOR CAUTION: The study is limited by a low response rate, the relatively small sample and the hypothetical nature of the decision, as clinician recommendations may have differed in an actual clinical setting. WIDER IMPLICATIONS OF THE FINDINGS: Our findings show that fertility history and use of ART may affect clinicians' recommendations regarding amniocentesis following receipt of screening test results. This raises the question of how subjective factors influence clinicians' decisions regarding other aspects of pregnancy management. STUDY FUNDING AND COMPETING INTEREST: There was no funding source to this study. The authors declare no conflicts of interest.

Effects of treatment of ectopic pregnancy with methotrexate or salpingectomy in the subsequent IVF cycle.

Ectopic pregnancy is a known risk for patients treated with IVF. The objective of this study was to evaluate the effect of methotrexate (MTX) and laparoscopic salpingectomy as treatments of ectopic pregnancy on ovarian response during IVF cycles. Data of all women treated for ectopic pregnancy as a result of IVF treatment were evaluated; the study included women who had an unruptured ectopic pregnancy after IVF treatment that was treated with either MTX or laparoscopic salpingectomy and underwent a subsequent IVF cycle. The main outcome measures were baseline serum FSH concentrations and ovarian response in the subsequent IVF cycle after treatment of ectopic pregnancy. Of a total of 58 patients, 36 were previously treated with MTX and 22 others by salpingectomy. No significant differences were observed between the MTX and the salpingectomy groups in the parameters of ovarian response in the subsequent IVF cycle.

Omega-shaped variant of the umbilical artery: prenatal diagnosis and outcome.

The purpose of this series was to report on the observation of an anomalous course of the umbilical artery. Ten cases in a 25-month period are reported. An omega-shaped variant, coined the "omega sign," of one of two umbilical arteries or of a single umbilical artery was observed. In 2 cases, there were two umbilical arteries, one of them with the anomalous vessel. In 8 cases, the vessel was a single umbilical artery. In 1 case with a single umbilical artery and pericardial effusion, aneuploidy was found on amniocentesis. A second case was associated with multiple anomalies. A third case was associated with hypoplastic left heart syndrome. Seven cases with the omega sign as an isolated finding, with or without a single umbilical artery, had favorable outcomes. An omega-shaped variant of the umbilical artery is likely to be more common in cases of a single umbilical artery than in cases with two umbilical arteries. It is probably a normal variant when unassociated with additional sonographically detectable structural anomalies.

DHEA supplementation may improve IVF outcome in poor responders: a proposed mechanism.

OBJECTIVE: Dehydroepiandrosterone (DHEA) supplementation for poor responders may improve ovarian response and IVF treatment outcome. This study aimed to determine the mechanism of action of DHEA, and specifically, the stage of folliculogenesis influenced by DHEA. STUDY DESIGN: This is a prospective, self-controlled study of poor responders to IVF treatment, comparing day 3 biochemical (anti-Mullerian hormone (AMH), inhibin B and FSH) and ultrasound (antral follicle count (AFC)) ovarian reserve markers and IVF treatment outcome before and after DHEA supplementation of at least 3 months duration. RESULTS: Thirty-two women were included. Following DHEA, there was a significant increase in AFC (P=0.0003) without significant changes in the baseline biochemical parameters AMH, inhibin B, or FSH. The enhanced response comprised increased peak estradiol levels (P=0.0005), number of follicles >15 mm, oocytes, MII oocytes and embryos (P=0.004, P=0.00001, P=0.0004 and P=0.0006, respectively) and oocytes number/total FSH dose (P=0.0009). The proportion of cancelled cycles due to very poor response decreased significantly (P=0.02). CONCLUSIONS: DHEA does not appear to exert influence via recruitment of pre-antral or very small antral follicles (no change in AMH and inhibin B) but rather by rescue from atresia of small antral follicles (increased AFC).

PGD for fragile X syndrome: ovarian function is the main determinant of success.

BACKGROUND: PGD for fragile X syndrome (FRAX) is inefficient, probably owing to fewer oocytes, poor embryo quality and difficulties in genetic analysis. We investigated IVF-PGD in FRAX mutation carriers compared with controls, looking at the effects of oocyte and embryo number/quality on live birth outcome. METHODS: We performed IVF-PGD in 27 patients with the FRAX mutation and 33 controls with other genetic diseases. Genetic testing was by multiplex PCR. RESULTS: Seventy-nine and 108 IVF-PGD cycles were started in FRAX mutation carriers and controls, respectively. Twenty-two patients had a premutation (CGG repeat number 60-200) and five had a full mutation (300-2000 CGG repeats). FRAX patients required higher doses of gonadotrophins (6788 ± 2379 versus 4360 ± 2330, P< 0.001) but had lower peak serum estradiol levels (8166 ± 5880 versus 10 211 ± 4673, P = 0.03) and fewer oocytes retrieved (9.8 ± 6 versus 14 ± 8, P = 0.01). The cancellation rate (unsatisfactory ovarian response) was higher in the FRAX group than in the control group (13 versus 1%, P < 0.001). When embryos were transferred, ongoing pregnancy/live birth rates per transfer were similar (29 versus 36%, P = 0.54). CONCLUSIONS: Ovarian dysfunction in FRAX carriers is more prevalent and profound than previously appreciated, with a high cancelation rate and reduced efficiency of PGD. The main determinant for successful PGD for FRAX is ovarian dysfunction. When embryo transfer is possible, the results are comparable to PGD for other monogenic diseases.