Overview
This lecture covers the basics of infertility: its definition and epidemiology, the four main aetiological categories (ovulatory, tubal/uterine/peritoneal, male factor, unexplained), the standard investigations used to work up a couple, and the treatment pathway from lifestyle and timing advice through ovulation induction, IUI, IVF/ICSI, donor gametes, preimplantation genetic testing and fertility preservation, all set within New Zealand’s funding and legal framework (CPAC, HART Act, ECART).
Definition and Epidemiology
- Infertility: inability to conceive or carry a baby to term following 1 year of unprotected intercourse.
- Affects 1 in 4 couples in Aotearoa.
- Can create profound emotional distress.
- Female age has a strong effect on monthly pregnancy rate: roughly flat around 25%/month from age 22-28, declines steadily through the 30s, drops sharply after ~36, and is close to 0% by age 44-46.
Aetiology of Infertility
Four roughly equal categories, ~25% each:
- Ovulation problems
- Tubal/uterine/peritoneal problems
- Male factor
- Unexplained
Ovulation Problems
- Polycystic ovarian syndrome (PCOS) accounts for 85% of ovulation problems.
- Other causes: hypothalamic amenorrhea, ovarian failure, elevated prolactin.
- Hypothalamic-pituitary-gonadal axis: hypothalamus releases GnRH (under negative feedback) to the anterior pituitary; the pituitary releases LH and FSH, which act on the testis/ovary; the testis produces testosterone and the ovary produces estrogen/progesterone; these sex steroids feed back negatively on the hypothalamus and pituitary.
Uterine, Peritoneal and Tubal Problems
- Uterine: fibroids, polyps, intrauterine adhesions, Mullerian anomalies.
- Septate uterus: a wedge of fibrous tissue divides the uterine cavity.
- Asherman’s syndrome: band-like adhesions cross the uterine lining.
- Bicornuate uterus: incomplete uniting of the uterus.
- Peritoneal: Endometriosis.
- Tubal: pelvic inflammatory disease, adhesions from major surgery or peritonitis.
Endometriosis and Fertility
Endometriosis reduces fertility through several parallel mechanisms:
- Endometrium: reduced endometrial receptivity, reduced HOXA10 expression.
- Peritoneal microenvironment: increased macrophage activity, increased TNF-alpha, IL-1beta, IL-6, IL-8.
- Sperm: immobilisation, DNA damage, reduced pooling, reduced binding.
- Anatomical distortion: dense or filmy adhesions; fimbrial blunting, clubbing, agglutination, phimosis; hydro/haematosalpinx.
- Ovary: endometriomata cause reduced oocyte numbers and reduced oocyte quality.
Male Factor Infertility
- Spermatogenesis: development of mature sperm, occurring in the testis under hypothalamic-pituitary-gonadal axis regulation (same axis diagrammed above: hypothalamus-GnRH-pituitary-LH/FSH-testis-testosterone).
- Carried out in the seminiferous tubules of the testis, then sperm are transported to the epididymis for storage and maturation, and pass via the vas deferens and ejaculatory duct (joined by the seminal vesicle) into the urethra, with prostate and bulbourethral gland contributions.
Disorders of sperm production/quality, by site:
- Pre-testicular: gonadotropin deficiency, high prolactin, thyroid dysfunction.
- Testicular: undescended testes, Klinefelter syndrome, chemotherapy, Y chromosome microdeletion.
- Post-testicular: vasectomy, epididymitis, CBAVD (congenital bilateral absence of the vas deferens), retrograde ejaculation.
Standard Infertility Investigations
- Full history of both partners: reproductive, sexual, medical, surgical, BMI.
- Bloodwork: AMH, TSH.
- Ultrasound (transvaginal).
- Semen analysis.
- Hysterosalpingogram (HSG): assesses tubal patency via dye spill from the tubes.
Semen analysis reference cut-offs (WHO laboratory manual, 2010):
| Variable | Cut-off |
|---|---|
| Sperm volume | >1.5 ml |
| Sperm concentration | >15 million/ml |
| Total sperm count | >39 million |
| Sperm progressive motility (A+B) | >32% |
| Sperm morphology | >4% |
| Sperm DNA fragmentation | <30% |
| Non-sperm cells | <1 million/ml |
Principles of Treatment and NZ Funding Access
- Fertility treatments can be successful but success is not guaranteed; female partner age strongly affects success rate.
- Goals of infertility evaluation: define the cause, outline the options with full explanation, and let the patient/partner decide on next steps.
- New Zealand uses a Clinical Priority Access Criteria (CPAC) scoring system to decide public funding eligibility for fertility treatment, prioritising couples with a low or zero chance of natural conception in whom treatment offers a reasonable chance of success.
- Criteria include: age of female partner, BMI, length of infertility.
- Underserved populations: single and same-sex couples, couples with unexplained infertility.
Treatment Ladder
- Clarify fertile window and coital frequency.
- Lifestyle modification (BMI, alcohol/vaping/smoking/drugs).
- Ovulation induction medications.
- Intrauterine insemination (IUI).
- In vitro fertilisation (IVF).
- Donor options (egg, sperm, uterus).
Intrauterine Insemination (IUI)
- Used for: mild sperm problems, unexplained infertility, social infertility.
- Procedure: a catheter/syringe delivers processed sperm through the cervix directly into the uterus.
IVF and ICSI
Seven-step pathway, in order:
- Ovarian hyperstimulation.
- Oocyte pick-up (OPU).
- Sperm processing.
- Egg fertilisation (Intracytoplasmic sperm injection (ICSI): a holding pipette stabilises the oocyte while a fine needle injects a single sperm).
- Embryo development (illustrated as an early embryo at 18.5 hours post-injection, progressing to blastocyst stage).
- Embryo transfer.
- Pregnancy.
IVF success falls steeply with maternal age. Birth rate per single egg-collection cycle (including use of frozen embryos within 6 months) is roughly 53-55% for age <=30-33, declines through the 30s, drops further after ~39-40, and is about 10% by 42-43 and about 3% by 45+.
Donor Options and Third-Party Reproduction (NZ)
- Options: donor eggs, donor sperm, donor embryo, surrogacy (donor uterus).
- Expands options for infertile couples, single people, and the LGBTQI+ community.
- All third-party reproduction in New Zealand is altruistic (non-commercial).
- Raises complex social issues and requires a thorough counselling process.
- The HART Act legally defines the pretreatment counselling requirements and the legal status of the resulting child.
- All cases of surrogacy and embryo donation, and certain cases of oocyte or sperm donation, require case-by-case approval by the Ethics Committee for Assisted Reproductive Technology (ECART).
Preimplantation Genetic Testing (PGT)
- Preimplantation genetic testing (PGT) screens embryos for genetic abnormalities before implantation in the uterus.
- PGT-M: for couples with an inheritable genetic disease, to prevent transmission of affected genes to offspring; NZ sets aside a small amount of government funding for PGT-M cycles each year.
- PGT-A: used where the risk of embryo aneuploidy is relatively high (recurrent miscarriage, or female partner >=38 years old); only privately offered in New Zealand.
Fertility Preservation (Eggs/Sperm)
- Emergent/urgent indications: prior to gonadotoxic chemotherapy; prior to removal of gonads.
- Social indication: commonly done to preserve younger, better-quality eggs for later use; not publicly funded.
- Oocyte retrieval procedure: ultrasound-guided transvaginal needle retrieval of oocytes from ovarian follicles.
Self-test
- Define infertility, including the time criterion used.
- What proportion of couples in Aotearoa are affected by infertility, and how does female age affect monthly pregnancy rate across the reproductive years?
- List the four aetiological categories of infertility with their approximate relative contributions.
- What is the most common cause of ovulatory infertility, and what other causes exist?
- Describe the steps of the hypothalamic-pituitary-gonadal axis, including where the negative feedback acts.
- Distinguish septate uterus, Asherman’s syndrome, and bicornuate uterus.
- Describe the mechanisms by which endometriosis reduces fertility, covering at least three different sites of action.
- List the three anatomical tiers of male factor infertility with two example causes for each.
- Describe the pathway sperm take from production to ejaculation, from seminiferous tubule to urethra.
- What semen analysis parameters and cut-offs define normal sperm concentration, motility, and morphology per the WHO 2010 manual?
- List the standard investigations performed in a couple presenting with infertility.
- What is the CPAC system, what criteria does it use, and which populations does the lecture identify as underserved by it?
- Describe the stepwise treatment ladder for infertility, from least to most invasive.
- For what indications is IUI used?
- Describe the seven steps of the IVF/ICSI pathway in order.
- Explain how IVF birth rate per egg collection changes with maternal age.
- What legal and ethical safeguards govern third-party reproduction in New Zealand?
- Distinguish PGT-M from PGT-A, including their respective indications and NZ funding status.
- What are the emergent/urgent versus social indications for fertility preservation, and how is oocyte retrieval performed?
Answers
Reveal answers
- Infertility is the inability to conceive or carry a baby to term following 1 year of unprotected intercourse.
- It affects 1 in 4 couples in Aotearoa. Monthly pregnancy rate is roughly flat around 25% from age 22-28, then declines steadily through the 30s, drops sharply after ~36, and is near 0% by 44-46.
- Ovulation problems (~25%), tubal/uterine/peritoneal problems (~25%), male factor (~25%), unexplained (~25%).
- PCOS causes 85% of ovulation problems; other causes are hypothalamic amenorrhea, ovarian failure, and elevated prolactin.
- The hypothalamus releases GnRH to the anterior pituitary (under negative feedback); the pituitary releases LH and FSH acting on the testis/ovary; the testis produces testosterone and the ovary produces estrogen/progesterone; these sex steroids feed back negatively on the hypothalamus and pituitary.
- Septate uterus: a fibrous wedge divides the uterine cavity. Asherman’s syndrome: band-like adhesions cross the uterine lining. Bicornuate uterus: incomplete uniting of the uterus.
- Endometrium: reduced receptivity and reduced HOXA10 expression. Peritoneal microenvironment: increased macrophage activity and inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-8). Sperm: immobilisation, DNA damage, reduced pooling/binding. Anatomical distortion: adhesions and fimbrial damage (blunting, clubbing, agglutination, phimosis, hydro/haematosalpinx). Ovary: endometriomata reduce oocyte number and quality.
- Pre-testicular: gonadotropin deficiency, high prolactin, thyroid dysfunction. Testicular: undescended testes, Klinefelter syndrome, chemotherapy, Y chromosome microdeletion. Post-testicular: vasectomy, epididymitis, CBAVD, retrograde ejaculation.
- Sperm are produced in the seminiferous tubules of the testis, pass to the epididymis for storage/maturation, then through the vas deferens and ejaculatory duct (joined by the seminal vesicle), through the prostate (with bulbourethral gland contribution), and out via the urethra.
- Sperm volume >1.5 ml, concentration >15 million/ml, total count >39 million, progressive motility (A+B) >32%, morphology >4%, DNA fragmentation <30%, non-sperm cells <1 million/ml.
- Full history of both partners (reproductive, sexual, medical, surgical, BMI), bloodwork (AMH, TSH), ultrasound, semen analysis, and hysterosalpingogram (HSG).
- CPAC (Clinical Priority Access Criteria) is New Zealand’s scoring system for public funding of fertility treatment, prioritising couples with low/zero natural conception chance where treatment offers a reasonable chance of success; criteria include female partner age, BMI, and length of infertility. Underserved populations named are single and same-sex couples, and couples with unexplained infertility.
- Clarify fertile window and coital frequency, then lifestyle modification (BMI, alcohol/vaping/smoking/drugs), then ovulation medications, then IUI, then IVF, then donor options.
- Mild sperm problems, unexplained infertility, and social infertility.
- Ovarian hyperstimulation, oocyte pick-up (OPU), sperm processing, egg fertilisation (ICSI), embryo development, embryo transfer, pregnancy.
- Birth rate per single egg-collection cycle is roughly 53-55% for age <=30-33, declines through the 30s, drops further after ~39-40, and reaches about 10% by 42-43 and about 3% by 45+.
- All third-party reproduction in NZ is altruistic; the HART Act legally defines pretreatment counselling requirements and the legal status of the child; all surrogacy and embryo donation, plus certain oocyte/sperm donation cases, require case-by-case ECART approval.
- PGT-M screens for a known inheritable genetic disease to prevent transmission to offspring, and receives limited NZ government funding. PGT-A screens for embryo aneuploidy, used when risk is relatively high (recurrent miscarriage or female partner >=38 years), and is only privately funded in NZ.
- Emergent/urgent: prior to gonadotoxic chemotherapy or gonad removal. Social: to preserve younger, better-quality eggs for later use (not publicly funded). Oocyte retrieval is performed by ultrasound-guided transvaginal needle aspiration of follicles.