The program for in vitro fertilization at Bourn Hall began in October 1980. Various types of infertility have been treated during this time using the natural menstrual cycle or stimulation of follicular growth with antiestrogens and gonadotrophins. Follicular growth and maturation are assayed by urinary estrogens and LH, monitored regularly during the later follicular stage. Many patients had an endogenous LH surge; others needed an injection of HCG to induce ovulation. All oocytes were recovered by laparoscopy. Wide variations occurred in the time interval between the start of the LH surge and oocyte recovery and between oocyte recovery and insemination. Embryos taken between the one- and the eight-cell stage were replaced into their mother, no standard procedure being adopted for all patients. The results of all treatments including patient's responses during the follicular and luteal phases, oocyte recovery, fertilization, cleavage, replacement, implantation, abortion, and birth and the effect of factors such as replacing two or more embryos, maternal age, and previous obstetric history are described in detail. The incidence of implantation after embryo replacement improved from 16.5% initially to 30% currently. More than 118 babies have been born, and many pregnancies are continuing.

Factors influencing the success of in vitro fertilization for alleviating human infertility

https://www.clevelandclinic.org/reproductiveresearchcenter/docs/agradoc344.pdf

The genetic causes of male factor infertility: A review

BACKGROUND The aim of this meta-analysis was to evaluate the association of progesterone elevation (PE) on the day of hCG administration with the probability of pregnancy in fresh, frozen-thawed and donor/recipient IVF cycles. METHODS A literature search in MEDLINE, SCOPUS, COCHRANE CENTRAL and ISI Web of Science was performed aiming to identify studies comparing the probability of pregnancy in patients with or without PE after ovarian stimulation with gonadotrophins and GnRH analogues. Standard meta-analytic methodology was used for the synthesis of results and meta-regression for exploration of heterogeneity. RESULTS Sixty-three eligible studies were identified evaluating 55 199 fresh IVF cycles, nine studies evaluating 7229 frozen-thawed cycles and eight studies evaluating 1330 donor/recipient cycles. In fresh IVF cycles, a decreased probability of pregnancy achievement was present in women with PE (when PE was defined using a threshold ≥ 0.8 ng/ml) when compared with those without PE. The pooled effect sizes were 0.8-1.1 ng/ml: odds ratio (OR) = 0.79; 1.2-1.4 ng/ml: OR = 0.67; 1.5-1.75 ng/ml: OR = 0.64; 1.9-3.0 ng/ml: OR: 0.68 (P < 0.05 in all cases). No adverse effect of PE on achieving pregnancy was observed in the frozen-thawed and the donor/recipient cycles. CONCLUSIONS Based on the analysis of more than 60 000 cycles, it can be supported that PE on the day of hCG administration is associated with a decreased probability of pregnancy achievement in fresh IVF cycles in women undergoing ovarian stimulation using GnRH analogues and gonadotrophins. On the other hand, an adverse effect of PE does not seem to be present in frozen-thawed and donor/recipient cycles.

/pdf/progesterone-elevation-and-probability-of-pregnancy-after-mrlhrsiz6m.pdf

Progesterone elevation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60 000 cycles

https://www.endo.theclinics.com/article/S0889-8529(05)70048-7/pdf

Gonadal damage from chemotherapy and radiotherapy.

BACKGROUND: Y chromosome microdeletions are associated with severe male factor infertility. In this study, the success rate of testicular sperm retrieval was determined for men with deletions of AZF regions a, b or c. METHODS: AZF deletions were detected by PCR of 30 sequence-tagged sites within Yq emphasizing the AZFa, b and c regions. Semen analysis and diagnostic testis biopsy or testicular sperm extraction (TESE) findings were correlated with the specific AZF region deleted. RESULTS: A total of 78 men with AZF deletions included three with AZFa deletion, 11 with AZFb, 42 with AZFc, 16 with AZFb+c and six with Yq (AZFa+b+c). All men with AZFa, AZFb, AZFb+c and Yq deletions were azoospermic and no sperm were found with TESE or biopsy. Of men with isolated AZFc deletion, sperm were found in 75% (9/12) by TESE and 45% (9/20) on biopsy (56% overall); 62% (26/42) were azoospermic and 38% (16/42) severely oligozoospermic. A total of 7 patients with deletion patterns that included the complete AZFa region and 23 that included the complete AZFb region who underwent TESE or biopsy did not have sperm detected by these surgical measures. CONCLUSIONS: Microdeletion of the entire AZFa or AZFb regions of the Y chromosome portends an exceptionally poor prognosis for sperm retrieval, whereas the majority of men with AZFc deletion have sperm within the semen or testes available for use in IVF/ICSI.

/pdf/detection-of-sperm-in-men-with-y-chromosome-microdeletions-32d8dv9xji.pdf

Detection of sperm in men with Y chromosome microdeletions of the AZFa, AZFb and AZFc regions

Oocytes and matched samples of follicular fluid were obtained from 156 pre-ovulatory follicles in 125 women 26--36 h after either administration of hCG or the onset of an endogenous LR surge. Concentrations of estradiol-17 beta (E2), progesterone (P) and androstenedione (A4) in the fluid of individual donor follicles were measured and related to the success of fertilisation of oocytes in vitro and the incidence of pregnancies after embryo transfer. Oocytes which gave rise to successful pregnancies were obtained from follicles which contained greater concentrations of E2 and a higher ratio of E2:P than did oocytes from which pregnancy did not result. These data provide direct evidence in support of the hypothesis that estrogenic follicles are the sole source of ova which undergo fertilisation and subsequently give rise to pregnancy in women.

Successful fertilisation of human oocytes in vitro: concentration of estradiol-17s, progesterone and androstenedione in the antral fluid of donor follicles.11

Presence of mature sperm in testicular parenchyma of men with nonobstructive azoospermia: prevalence and predictive factors.

Microsurgical epididymal sperm aspiration was a great advance in the therapy of patients with non-reconstructable, obstructive azoospermia, most notably congenital bilateral absence of the vas deferens. Using conventional in-vitro fertilization, pregnancies were rarely achieved because the rate of oocyte fertilization was extremely poor. However, the use of retrieved spermatozoa in conjunction with intracytoplasmic sperm injection (ICSI) has dramatically increased the likelihood of embryo formation. Typically, sperm and oocyte harvesting are performed simultaneously. We have investigated whether frozen-thawed spermatozoa work as well as fresh spermatozoa. When we had concluded from our own population of patients (groups I and II) that they did, we adopted a policy of aspirating spermatozoa, primarily cryopreserving them and using them for ICSI at a later date. We found the fertilization rates of this latter cohort of patients (group III) to be excellent (37% per oocyte), and the ongoing pregnancy rate is quite satisfactory (40% per couple, 29% per cycle). We offer this approach as an alternative to the traditional scheme because it markedly eases the burden of partner scheduling on both the couple and the clinicians involved. In addition, assurance of the availability of male partner spermatozoa can be attained prior to beginning ovulation induction.

/pdf/efficacy-of-intracytoplasmic-sperm-injection-using-18e4zlegig.pdf

Efficacy of intracytoplasmic sperm injection using intentionally cryopreserved epididymal spermatozoa

Premature luteinization and in vitro fertilization outcome in gonadotropin/gonadotropin-releasing hormone antagonist cycles in women with polycystic ovary syndrome.

Ronald Carson

Papers

Successful fertilisation of human oocytes in vitro: concentration of estradiol-17s, progesterone and androstenedione in the antral fluid of donor follicles.11

Presence of mature sperm in testicular parenchyma of men with nonobstructive azoospermia: prevalence and predictive factors.

Efficacy of intracytoplasmic sperm injection using intentionally cryopreserved epididymal spermatozoa

Premature luteinization and in vitro fertilization outcome in gonadotropin/gonadotropin-releasing hormone antagonist cycles in women with polycystic ovary syndrome.

Absence of deleted in azoospermia (DAZ) genes in spermatozoa of infertile men with somatic DAZ deletions.