In vitro maturation (IVM) of human immature oocytes: is it still relevant?

In vitro maturation (IVM) of human immature oocytes has been shown to be a viable option for patients at risk of ovarian hyperstimulation syndrome (OHSS), those seeking urgent fertility preservation and in circumstances where controlled ovarian stimulation is not feasible. Moreover, IVM techniques can be combined with ovarian tissue cryobanking to increase the chances of conception in cancer survivors. The clinical applications of IVM in the field of reproductive medicine are rapidly expanding and the technique is now classified as non-experimental. In contrast to conventional IVF (in vitro fertilization), IVM offers several advantages, such as reduced gonadotropin stimulation, minimal risk of ovarian hyperstimulation syndrome (OHSS), reduced treatment times and lower costs. However, the technical expertise involved in performing IVM and its lower success rates compared to traditional IVF cycles, still pose significant challenges. Despite recent advances, such as innovative biphasic IVM systems, IVM is still an evolving technique and research is ongoing to refine protocols and identify techniques to improve its efficiency and effectiveness. A comprehensive understanding of the distinct mechanisms of oocyte maturation is crucial for obtaining more viable oocytes through in vitro methods, which will in turn lead to significantly improved success rates. In this review, the present state of human IVM programs and future research directions will be discussed, aiming to promote a better understanding of IVM and identify potential strategies to improve the overall efficiency and success rates of IVM programs, which will in turn lead to better clinical outcomes.

Should IUI replace IVF as first-line treatment for unexplained infertility? A literature review.

BACKGROUND: Unexplained infertility accounts for 25% of infertility causes in the UK. Active intervention methods, such as intrauterine insemination (IUI) or in vitro fertilisation (IVF), are often sought. Despite the National Institute for Health and Care Excellence (NICE) recommending IVF for unexplained infertility, this recommendation has generated an ongoing debate, with few fertility clinics discontinuing the use of IUI as the first-line management of choice. In contrast to NICE, recent guidance released from the European Society for Human Reproduction and Embryology (ESHRE) in August 2023 supports the use of IUI as first-line. High-quality evidence behind such interventions is lacking, with current literature providing conflicting results. AIMS: This review aims to provide a literature overview exploring whether IUI or IVF should be used as first-line treatment for couples with unexplained infertility, in the context of current guidelines. METHODS: The primary outcome used to assess efficacy of both treatment methods is live birth (LB) rates. Secondary outcomes used are clinical pregnancy (CP) and ongoing pregnancy (OP) rates. A comprehensive literature search of 4 databases: Ovid MEDLINE, EMBASE, Maternity & Infant Care and the Cochrane Library were searched in January 2022. Upon removal of duplications, abstract screening, and full-text screening, a total of 34 papers were selected. DISCUSSION/CONCLUSION: This review highlights a large discrepancy in the literature when examining pregnancy outcomes of IUI and IVF treatments. Evidence shows IUI increases LB and CP rates 3-fold compared to expectant management. Literature comparing IUI to IVF is less certain. The review finds the literature implies IVF should be used for first-line management but the paucity of high-quality randomised controlled trials (RCTs), coupled with heterogeneity of the identified studies and a lack of research amongst women > 40 years warrants the need for further large RCTs. The decision to offer IUI with ovarian stimulation (IUI-OS) or IVF should be based upon patient prognostic factors. We suggest that IUI-OS could be offered as first-line treatment for unexplained infertility for women < 38 years, with good prognosis, and IVF could be offered first to those > 38 years. Patients should be appropriately counselled to enable informed decision making.

Spinal cord stimulation during the antepartum and intrapartum periods: a case report showing no deleterious effect of conventional paraesthesia producing stimulation.

We report on a 25-year-old woman who used her spinal cord stimulator (SCS), previously inserted for chronic regional pain syndrome (CPRS), to assist with both chronic and pregnancy-related pain management. We describe the therapeutic effect of the stimulator and briefly highlight the issues surrounding the use of SCS during pregnancy.

In-vitro maturation versus IVF with GnRH antagonist for women with polycystic ovary syndrome: treatment outcome and rates of ovarian hyperstimulation syndrome.

In-vitro maturation (IVM) treatment has gained popularity for decreasing the incidence of ovarian hyperstimulation syndrome (OHSS) by eliminating or minimizing the use of gonadotrophins in women with polycystic ovary syndrome (PCOS). Studies have shown that IVF with GnRH-antagonist protocol is associated with a lower incidence of OHSS. Data comparing the relative success of these two treatments is, however, lacking. Treatment outcome and rates of OHSS were compared in patients with PCOS who underwent assisted conception with either IVM or IVF with GnRH-antagonist protocol between 2006 and 2011. The number of oocytes retrieved was higher in the IVM group, whereas the number of mature oocytes, fertilization rate and number of embryos cleaved were comparable. The implantation rate was higher in the IVF group. The clinical pregnancy rates per embryo transfer were not statistically different (IVF: 45.8% versus IVM: 32.4%). The live-birth rate was higher in the IVF group (IVF: 40.7% versus IVM: 23.5%; P = 0.04). Five women developed moderate or severe OHSS in the IVF group, whereas none did in the IVM group. Both IVM and IVF with GnRH-antagonist protocol seem to be effective treatment regimens in women with PCOS, although IVM is associated with a lower risk of OHSS.

Pregnancy after endometrial ablation. A report of three cases.

BACKGROUND: Pregnancies after endometrial ablation (EA) are rare and are associated with high morbidity, especially in the second and third trimesters. CASE: We report 3 cases of pregnancy after EA in which severe complications occurred during the first trimester. The first case concerns an unexpected pregnancy after EA in a 50-year-old woman. Hysterectomy via laparotomy was needed because of heavy bleeding and severe anemia. Pathology showed a complete hydatidiform mole without invasion. Ultrasound-guided in situ methotrexate injection could be a nonsurgical alternative to terminate an intrauterine pregnancy after EA when the pregnancy is located within uterine synechiae, as shown by the second case. The third case presented as an accreta placentation mimicking hyperplastic myometrial invasion in a 46-year-old patient. CONCLUSION: Because of the high morbidity of these pregnancies that could still occur after EA, patients need contraception after EA, and concomitant hysteroscopic sterilization should be proposed at the same time.

Fertilization, embryo development, and clinical outcome of immature oocytes obtained from natural cycle in vitro fertilization.

PURPOSE: To analyze the fertilization, embryo development, and clinical outcome of immature oocytes obtained from natural cycle IVF in women with regular cycles. METHODS: Natural cycle IVF was performed in 28 patients who had normal ovaries, > 6 antral follicle counts and were less than 40 years old (n=28 cycles). An hCG trigger of 10,000 IU was administered 36 h before oocyte collection when the diameter of the dominant follicle (DF) was over 12 mm. Oocytes were retrieved from DF as well as from the cohort of smaller follicles. Embryological aspects of the mature and immature oocytes retrieved from these cycles as well as the implantation and clinical pregnancy rates depending on the origin of the embryos transferred were evaluated. RESULT(S): Overall clinical pregnancy and implantation rates were 20.8 % and 6.7 %, respectively. There were no differences in in vitro maturation (IVM), fertilization and embryo development between immature oocytes retrieved with and without in vivo matured oocytes. However, the clinical and implantation rates in cycles with embryos produced from in vivo matured oocytes transferred were better than the cycles where only IVM embryos were transferred (30.8 %, 9.1 % vs. 9.1 %, 3.2 %). CONCLUSION(S): Although our results show that immature oocytes from natural cycle IVF can fertilize normally and can be used to increase the number of embryos available for transfer, the embryos derived from the immature oocytes in natural cycles IVF have a poorer reproductive potential.

High prevalence of isolated sperm DNA damage in infertile men with advanced paternal age.

BACKGROUND: Sperm DNA damage is associated with male infertility, lower pregnancy rates and pregnancy loss. OBJECTIVE: The primary aim of our study was to evaluate the prevalence of sperm DNA damage in younger and older men with normozoospermia. DESIGN, SETTING AND PARTICIPANTS: We obtained semen from 277 consecutive non-azoospermic men presenting for sperm DNA testing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main outcome measures included sperm % DNA fragmentation index (%DFI, using sperm chromatin structure assay), sperm concentration, motility and morphology, and, paternal age. RESULTS AND LIMITATIONS: Sperm % DFI was positively correlated with paternal age (r = 0.20, P < 0.001) and inversely correlated % progressive motility (r = -0.16, P = 0.01). Sperm %DFI was significantly higher in older (≥40 years) compared to younger (<40 years) normozoospermic men (17 ± 13 vs. 12 ± 8, respectively P = 0.008), whereas, sperm concentration, progressive motility and morphology were not significantly different in these two groups. Moreover, the prevalence of high levels of sperm DNA damage (>30 % DFI) was significantly higher in older compared to younger normozoospermic men (17 % vs. 3 %, respectively, P < 0.001). CONCLUSION: The data indicate that a conventional semen analysis can often fail to detect a defect in spermatogenesis (high %DFI) in older men and suggest that infertile couples with advanced paternal age, including those with normal semen parameters, should consider sperm DNA testing as part of the couple evaluation.

Ovarian reserve and response to IVF and in vitro maturation treatment following chemotherapy.

BACKGROUND: Chemotherapy and radiotherapy can result in ovarian failure and premature menopause. However, there is still a paucity of information on the ovarian reserve and efficacy of assisted reproduction treatment (ART) procedures in patients with cancer previously exposed to chemotherapy or radiotherapy. The aim of our study was to evaluate the ovarian reserve and ovarian response to IVF or in vitro maturation (IVM) treatment in women who had previously been treated with chemotherapy. METHODS: In this retrospective cohort study, we compared 23 women with cancer who had undergone chemotherapy and subsequently underwent fertility treatment with IVF (n=14) or IVM (n=9). In the IVF group, patients mostly had hematologic, gynecologic, gastro-intestinal, bone and soft tissue cancers, whereas in the IVM group patients had estrogen-receptor positive breast cancer, hematologic and brain cancers. The control (unexposed) group consisted of 70 age-matched women with male factor infertility undergoing the same treatment protocol (IVF n=42 and IVM n=28). All women were aged<42 years and undergoing their first cycle of ART. RESULTS: There were no differences in age and FSH levels between the cancer and the control groups. However, the antral follicle count (AFC) was lower in the cancer-IVF group (median: 5, range: 3-12) than in the control group (median: 15, range: 12-18; P=0.0009). Women with cancer treated with IVF had lower peak estradiol levels on the day of hCG administration than controls (P=0.006) and lower number of oocytes retrieved [median: 4.5, range: 2-7; versus 12 (8-16) in controls; P<0.0001]. In patients with cancer treated with IVM, the AFC was lower than in the control group (median: 14, range: 9.5-17; versus median: 20.5 range: 16-23, respectively; P=0.0007). Likewise, the number of oocytes retrieved was lower in the cancer-IVM group (median: 6, range: 4-10) than that in the control group (median 10.5, range: 7.5-17; P=0.01). The percentage of mature metaphase II oocytes was comparable in the cancer and control groups. CONCLUSIONS: The ovarian reserve, response to gonadotrophins and number of oocytes retrieved are adversely affected by previous chemotherapy. This study reports the first series of IVM outcomes in cancer patients with a prior history of chemotherapy. In women with estrogen-receptor positive breast cancer, IVM of oocytes with cryopreservation of oocytes or embryos is a viable option. Since the efficacy of ART is significantly reduced after chemotherapy, early referral for fertility preservation before gonadotoxic treatment will give these young women the best chance to conceive.

Ovarian stimulation and intrauterine insemination in women aged 40 years or more.

Fertility decreases with advancing age. This study retrospectively reviewed the results of ovarian stimulation and intrauterine insemination (IUI) in women 40 years old with diminished ovarian reserve or unexplained infertility who underwent treatment with ovarian stimulation/IUI with clomiphene citrate or gonadotrophin and compared them with the results of IVF and in-vitro maturation (IVM) treatments. The main outcome measures were pregnancy and live-birth rates. The profiles of the patients in ovarian stimulation, IVM and IVF groups were comparable. There were no clinical pregnancies in the clomiphene citrate and IVM groups. The clinical-pregnancy rates in the gonadotrophin and IVF groups were 2.6% and 16.9% and the live-birth rates were 2.6% and 13.7%, respectively. Compared with ovarian stimulation, IVF is most effective for women aged 40 years or more. Attempting success with ovarian stimulation or IVM will delay conception unnecessarily.

Recurrent implantation failure: gamete and embryo factors.

Chromosomal abnormalities, sperm DNA damage, zona hardening, inadequate culture conditions, and suboptimal embryo development all play a significant role in the etiology of recurrent implantation failure. Evidence suggests that preimplantation genetic screening does not increase implantation or live birth rates. Comparative genomic hybridization array and analysis of single nucleotide polymorphisms could enable a more comprehensive screening of chromosomes. Assisted hatching may help to overcome zona hardening in selected cases. Optimal culture conditions and blastocyst transfer could contribute toward improving implantation and pregnancy rates. Novel embryo assessment and selection procedures, such as time-lapse imaging and metabolomics, may help in better evaluation of embryo quality and viability and help in selecting embryos with the highest implantation potential. The safety and efficacy of emerging treatment modalities should be evaluated in prospective randomized clinical trials before being applied in routine clinical practice.

Ovarian reserve, response to gonadotropins, and oocyte maturity in women with malignancy.

OBJECTIVE: To study the ovarian reserve, ovarian response to gonadotropins, and oocyte maturity in women with cancer undergoing in vitro fertilization (IVF) before chemotherapy or radiotherapy. DESIGN: Case-control study. SETTING: University teaching hospital. PATIENT(S): We evaluated all women with malignancy who underwent fertility preservation from the year 2003 to 2010. We compared 41 women with cancer undergoing IVF treatment with a control group of 48 age-matched women undergoing IVF for male factor infertility with the same protocol. INTERVENTION(S): In vitro fertilization. MAIN OUTCOME MEASURES(S): Ovarian reserve, ovarian response to gonadotropins, number of oocytes retrieved, and oocyte maturity. RESULT(S): There were no significant differences in age, antral follicle count, serum FSH, total dose of gonadotropins required for stimulation, duration of stimulation, or peak E(2) levels on the day of hCG administration between women with cancer and the control group. No significant differences were observed in the number of retrieved oocytes between the malignancy and control groups. The percentages of mature oocytes in patients with hematologic malignancy (83.3%), gynecologic and intestinal malignancy (94%), and brain cancer (86%) and in the control group (82.1%) were similar, as were the fertilization rates. CONCLUSION(S): In young women with malignancy, ovarian reserve, response to gonadotropins, oocytes retrieved, and oocyte maturity remain unaltered by the neoplastic process. This is in contrast to the impairment of spermatogenesis before therapy in men with cancer.

Ovarian reserve and oocyte maturity in women with malignancy undergoing in vitro maturation treatment.

OBJECTIVE: To evaluate ovarian reserve and oocyte maturity in women with malignancy. DESIGN: A case-control study. SETTING: University teaching hospital. PATIENT(S): We evaluated all women with malignancy who underwent in vitro maturation treatment for fertility preservation from the year 2003 to 2009. The results were compared with those of an age-matched infertile control group. INTERVENTION(S): In vitro maturation treatment. MAIN OUTCOME MEASURE(S): Ovarian reserve and oocyte maturity. RESULT(S): Women with malignancy of the breast (n = 87), hematologic malignancy (n = 16), gynecologic or abdominal malignancy (n = 9), and other malignancies (n = 16) were compared with infertile control women (n = 79). The age was similar in all groups except in women with hematologic malignancy where they were younger than the control group (24.9 ± 1.1 years vs. 30.8 ± 0.4 years, confidence interval 4.0-9.5). Baseline FSH in this group was also lower than in the control group. Women with breast cancer had a lower number of retrieved oocytes than the control group (95% confidence interval 0-5). There were no significant differences in antral follicle count, percentage of mature oocytes on collection day, and percentage of metaphase II oocytes matured in vitro among all groups of women. CONCLUSION(S): Women with breast cancer have fewer numbers of retrieved oocytes than infertile controls. Ovarian reserve and oocyte maturity in other types of malignancy are similar to those in the control group.

Referral patterns for pelvic floor disorders.

INTRODUCTION AND HYPOTHESIS: To determine referral patterns to the gynecology directorate for symptomatic pelvic organ prolapse and urinary incontinence METHODS: A prospective multicenter survey of three district general hospitals in Northwest England. Referral letters sent by family physicians to consultants were studied over a three-month period. Main outcome measures were presenting complaints of prolapse and incontinence RESULTS: Two thousand seven hundred sixty-nine referral letters were surveyed. Urogynecological complaints (18.4%) were the second most common reason for referral. Menstrual irregularities (21.9%) were the commonest presenting complaint. Among these urogynecology referrals, 38.4% (196/510) were for urinary incontinence (UI), 36.2% (185/510) were for symptomatic prolapse (POP), and 25.3% (129/510) were referred with combined complaints of POP and UI. Of all urogynecological referrals, 56% were for women below 60 years of age. Twenty percent of those with urogynecological complaints had undergone prior hysterectomy. CONCLUSIONS: Pelvic floor disorders were the second most common reason for referral to gynecologists.